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Skrindo, Ingebjørg; Ballke, Karin Christina; Gran, Einar; Johansen, Finn-Eirik; Bækkevold, Espen Sønderaal & Jahnsen, Frode Lars
(2015).
IL-5 production by resident mucosal allergen-specific T cells in an explant model of allergic rhinitis.
Clinical and Experimental Allergy.
ISSN 0954-7894.
45(8),
p. 1296–1304.
doi:
10.1111/cea.12543.
-
-
Melum, Guro Reinholt; Farkas, Lorant; Scheel, Cecilie; van Dieren, Brenda; Gran, Einar & Liu, YJ
[Show all 9 contributors for this article]
(2014).
A thymic stromal lymphopoietin-responsive dendriticcell subset mediates allergic responses in the upper airway mucosa.
Journal of Allergy and Clinical Immunology.
ISSN 0091-6749.
134(3),
p. 613–621.
doi:
10.1016/j.jaci.2014.05.010.
-
-
Reikvam, Dag Henrik; Derrien, Muriel; Islam, Rejoanoul; Erofeev, Alexander; Grcic, Vedrana & Sandvik, Anders
[Show all 11 contributors for this article]
(2012).
Epithelial-microbial crosstalk in polymeric Ig receptor deficient mice.
European Journal of Immunology.
ISSN 0014-2980.
42(11),
p. 2959–2970.
doi:
10.1002/eji.201242543.
-
Khnykin, Denis; Rønnevig, Jørgen Rikard; Johnsson, Margareta; Sitek, Jan Cezary; Blaas, Harm-Gerd Karl & Hausser, Ingrid
[Show all 8 contributors for this article]
(2012).
Ichthyosis prematurity syndrome: Clinical evaluation of 17 families with a rare disorder of lipid metabolism.
Journal of American Academy of Dermatology.
ISSN 0190-9622.
66(4),
p. 606–616.
doi:
10.1016/j.jaad.2011.04.014.
-
Johansen, Finn Eirik & Kaetzel, CS
(2011).
Regulation of the polymeric immunoglobulin receptorand IgA transport: new advances in environmental factors that stimulate pIgR expression and its role in mucosal immunity.
Mucosal Immunology.
ISSN 1933-0219.
4(6),
p. 598–602.
doi:
10.1038/mi.2011.37.
-
Bruno, M.E.C.; Frantz, A.L.; Rogier, E.W.; Johansen, Finn Eirik & Kaetzel, C.S.
(2011).
Regulation of the polymeric immunoglobulin receptor by the classical and alternative NF-kappa B pathways in intestinal epithelial cells.
Mucosal Immunology.
ISSN 1933-0219.
4(4),
p. 468–478.
doi:
10.1038/mi.2011.8.
-
Skrindo, Ingebjørg; Scheel, Cecilie; Johansen, Finn Eirik & Jahnsen, Frode Lars
(2011).
Experimentally induced accumulation of Foxp3(+) T cells in upper airway allergy.
Clinical and Experimental Allergy.
ISSN 0954-7894.
41(7),
p. 954–962.
doi:
10.1111/j.1365-2222.2011.03710.x.
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Søyland, Elisabeth; Heier, Ingvild; Rodríguez-Gallego, Carlos; Mollnes, Tom Eirik; Johansen, Finn Eirik & Holven, Kirsten Bjørklund
[Show all 12 contributors for this article]
(2011).
Sun exposure induces rapid immunological changes in skin and peripheral blood in patients with psoriasis.
British Journal of Dermatology.
ISSN 0007-0963.
164(2),
p. 344–355.
doi:
10.1111/j.1365-2133.2010.10149.x.
-
Duc, Mélanie; Johansen, Finn Eirik & Corthesy, B.
(2010).
Antigen Binding to Secretory Immunoglobulin A Results in Decreased Sensitivity to Intestinal Proteases and Increased Binding to Cellular Fc Receptors.
Journal of Biological Chemistry.
ISSN 0021-9258.
285(2),
p. 953–960.
doi:
10.1074/jbc.M109.059220.
-
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Strønen, Erlend; Abrahamsen, Ingerid Weum; Gaudernack, Gustav; Waelchli, Sebastien; Munthe, Else & Buus, S
[Show all 9 contributors for this article]
(2009).
Dendritic Cells Engineered to Express Defined Allo-HLA Peptide Complexes Induce Antigen-specific Cytotoxic T Cells Efficiently Killing Tumour Cells.
Scandinavian Journal of Immunology.
ISSN 0300-9475.
69(4),
p. 319–328.
doi:
10.1111/j.1365-3083.2008.02223.x.
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Hol, Johanna; Kuchler, Axel Matthias; Dalhus, Bjørn; Johansen, Finn Eirik; Haraldsen, Guttorm & Øynebråten, Inger
(2009).
Molecular Requirements for Sorting of the Chemokine Interleukin-8/CXCL8 to Endothelial Weibel-Palade Bodies.
Journal of Biological Chemistry.
ISSN 0021-9258.
284(35),
p. 23532–23539.
doi:
10.1074/jbc.M900874200.
-
-
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Ghumra, A; Shi, J; McIntosh, RS; Rasmussen, Ingunn B; Braathen, Ranveig & Johansen, Finn Eirik
[Show all 13 contributors for this article]
(2009).
Structural requirements for the interaction of human IgM and IgA with the human Fc alpha/mu receptor.
European Journal of Immunology.
ISSN 0014-2980.
39(4),
p. 1147–1156.
doi:
10.1002/eji.200839184.
-
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Qiao, Shuo Wang; Kobayashi, K; Johansen, Finn Eirik; Sollid, Ludvig Magne; Andersen, Jan Terje & Milford, E
[Show all 9 contributors for this article]
(2008).
Dependence of antibody-mediated presentation of antigen on FcRn.
Proceedings of the National Academy of Sciences of the United States of America.
ISSN 0027-8424.
105,
p. 9337–9342.
doi:
10.1073/pnas.0801717105.
-
-
Ghumra, A; Semblat, JP; McIntosh, RS; Raza, A; Rasmussen, Ingunn B & Braathen, Ranveig
[Show all 11 contributors for this article]
(2008).
Identification of residues in the C mu 4 domain of polymeric IgM essential for interaction with Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1).
Journal of Immunology.
ISSN 0022-1767.
181,
p. 1988–2000.
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Skrindo, Ingebjørg; Farkas, Lorant; Kvale, Espen Østhagen; Johansen, Finn Eirik & Jahnsen, Frode Lars
(2008).
Depletion of CD4(+)CD25(+)CD127(lo) regulatory T cells does not increase allergen-driven T cell activation.
Clinical and Experimental Allergy.
ISSN 0954-7894.
38(11),
p. 1752–1759.
doi:
10.1111/j.1365-2222.2008.03081.x.
-
-
Brandtzæg, Per & Johansen, Finn Eirik
(2007).
IgA and intestinal homeostasis.
In Kaetzel, CS (Eds.),
Mucosal Immune Defense: Immunoglobulin A.
Springer Science+Business Media B.V..
ISSN 978-0-387-72231-3.
p. 221–268.
-
Johansen, Finn Eirik; Braathen, Ranveig; Munthe, Else; Schjerven, Hilde & Brandtzæg, Per
(2007).
Regulation of the mucosal IgA system.
In Kaetzel, CS (Eds.),
Mucosal Immune Defense: Immunoglobulin A.
Springer Science+Business Media B.V..
ISSN 978-0-387-72231-3.
p. 111–143.
-
Braathen, Ranveig; Hohman, VS; Brandtzæg, Per & Johansen, Finn Eirik
(2007).
Secretory antibody formation: Conserved binding interactions between J chain and polymeric Ig receptor from humans and amphibians.
Journal of Immunology.
ISSN 0022-1767.
178,
p. 1589–1597.
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Sandvik, Anders; Wang, Yun Yong; Morton, Hugh Craig; Aasen, Ansgar Oddne; Wang, JE & Johansen, Finn Eirik
(2007).
Oral and systemic administration of beta-glucan protects against lipopolysaccharide-induced shock and organ injury in rats.
Clinical and Experimental Immunology.
ISSN 0009-9104.
148.
doi:
10.1111/j.1365-2249.2006.03320.x.
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Johansen, Finn Eirik; Yen, Elizabeth; Dickinson, Bonnie; Yoshida, Massaru; Claypool, Steve & Blumberg, Richard S
[Show all 7 contributors for this article]
(2006).
Biology of Gut Immunoglobulins.
In Johnson, Leonard (Eds.),
Physiology of the gastrointestinal tract, 1-2.
Elsevier.
ISSN 978-0-12-088394-3.
-
Braathen, Ranveig; Sandvik, Anders; Berntzen, Gøril; Hammerschmidt, S; Fleckenstein, Burkhard & Sandlie, Inger
[Show all 9 contributors for this article]
(2006).
Identification of a polymeric Ig receptor binding phage-displayed peptide that exploits epithelial transcytosis without dimeric IgA competition.
Journal of Biological Chemistry.
ISSN 0021-9258.
281,
p. 7075–7081.
Full text in Research Archive
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Davids, Barbara J; Palm, JE Daniel; Housley, Michael P; Smith, Jennifer R; Andersen, Yolanda S & Martin, Martin G
[Show all 11 contributors for this article]
(2006).
Polymeric immunoglobulin receptor in intestinal immune defense against the lumen-dwelling protozoan parasite Giardia.
Journal of Immunology.
ISSN 0022-1767.
177,
p. 6281–6290.
-
Michalek, S; Russell, M; Kaetzel, C & Johansen, Finn Eirik
(2006).
pIgR/IgA Sessions I and II: Summary.
Mucosal Immunology Update.
ISSN 1068-7629.
14(2),
p. 8–9.
-
Brandtzæg, Per; Johansen, Finn Eirik; Bækkevold, Espen Sønderaal & Farstad, Inger Nina
(2005).
Lacrimal glands: role in mucosal immunity compared with other secretory effector sites.
In Zierhut, Manfred; Stern, Michael E & Sullivan, David A (Ed.),
Immunology of the Lacrimal Gland, Tear Film and Ocular Surface.
Taylor and Francis.
ISSN 184184568X.
p. 1–11.
-
Brandtzæg, Per & Johansen, Finn Eirik
(2005).
Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties.
Immunological Reviews.
ISSN 0105-2896.
206,
p. 32–63.
-
Johansen, Finn Eirik; Bækkevold, Espen Sønderaal; Carlsen, Hege Synnøve; Farstad, Inger Nina; Soler, Dulce & Brandtzæg, Per
(2005).
Regional induction of adhesion molecules and chemokine receptors explains disparate homing of human B cells to systemic and mucosal effector sites: dispersion from tonsils.
Blood.
ISSN 0006-4971.
106,
p. 593–600.
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Schneeman, TA; Bruno, M; Schjerven, Hilde; Johansen, Finn Eirik; Chady, L & Kaetzel, CS
(2005).
Regulation of the polymeric Ig receptor by signaling through TLRs 3 and 4: linking innate and adaptive immune responses.
Journal of Immunology.
ISSN 0022-1767.
175,
p. 376–384.
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Uren, TK; Wijburg, OLC; Simmons, C; Johansen, Finn Eirik; Brandtzæg, Per & Strugnell, RA
(2005).
Vaccine-induced protection against gastrointestinal bacterial infections in the absence of secretory antibodies.
European Journal of Immunology.
ISSN 0014-2980.
35,
p. 180–188.
-
Øynebråten, Inger; Barois, Nicolas; Hagelsteen, Kathrine; Johansen, Finn Eirik; Bakke, Oddmund & Haraldsen, Guttorm
(2005).
Characterization of a novel chemokine-containing storage granule in endothelial cells: evidence for preferential exocytosis mediated by protein kinase A and diacylglycerol.
Journal of Immunology.
ISSN 0022-1767.
175(8),
p. 5358–5369.
Show summary
We have recently shown that several proinflammatory chemokines can be stored in secretory granules of endothelial cells (ECs). Subsequent regulated exocytosis of such chemokines may then enable rapid recruitment of leukocytes to inflammatory sites. Although IL-8/CXCL8 and eotaxin-3/CCL26 are sorted to the rod-shaped Weibel-Palade body (WPB), we found that GROalpha/CXCL1 and MCP-1/CCL2 reside in small granules that, similarly to the WPB, respond to secretagogue stimuli. In the present study, we report that GROalpha and MCP-1 colocalized in 50- to 100-nm granules, which occur throughout the cytoplasm and at the cell cortex. Immunofluorescence confocal microscopy revealed no colocalization with multimerin or tissue plasminogen activator, i.e., proteins that are released from small granules of ECs by regulated exocytosis. Moreover, the GROalpha/MCP-1-containing granules were Rab27-negative, contrasting the Rab27-positive, WPB. The secretagogues PMA, histamine, and forskolin triggered distinct dose and time-dependent responses of GROalpha release. Furthermore, GROalpha release was more sensitive than IL-8 release to inhibitors and activators of PKA and PKC but not to an activator of Epac, a cAMP-regulated GTPase exchange factor, indicating that GROalpha release is regulated by molecular adaptors different from those regulating exocytosis of the WPB. On the basis of these findings, we designated the GROalpha/MCP-1-containing compartment the type 2 granule of regulated secretion in ECs, considering the WPB the type 1 compartment. In conclusion, we propose that the GROalpha/MCP-1-containing type 2 granule shows preferential responsiveness to important mediators of EC activation, pointing to the existence of selective agonists that would allow differential release of selected chemokines.
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Dai, Kezheng; Johansen, Finn Eirik; Kolltveit, Kristin Melkevik; Aasheim, Hans-Christian; Dembic, Zlatko & Vartdal, Frode
[Show all 7 contributors for this article]
(2004).
Transcriptional activation of the SH2D2A gene is dependent on a cyclic adenosine 5'-monophosphate-responsive element in the proximal SH2D2A promoter.
Journal of Immunology.
ISSN 0022-1767.
172,
p. 6144–6151.
Show summary
The SH2D2A gene, encoding the T cell-specific adapter protein (TSAd), is rapidly induced in activated T cells. In this study we investigate the regulation of the SH2D2A gene in Jurkat T cells and in primary T cells. Reporter gene assays demonstrated that the proximal 1-kb SH2D2A promoter was constitutively active in Jurkat TAg T cells and, to a lesser extent, in K562 myeloid cells, Reh B cells, and 293T fibroblast cells. The minimal SH2D2A promoter was located between position -236 and -93 bp from the first coding ATG, and transcriptional activity in primary T cells depended on a cAMP response element (CRE) centered around position -117. Nuclear extracts from Jurkat TAg cells and activated primary T cells contained binding activity to this CRE, as observed in an EMSA. Consistent with this observation, we found that a cAMP analog was a very potent inducer of SH2D2A mRNA expression in primary T cells as measured by real-time RT-PCR. Furthermore, activation of SH2D2A expression by CD3 stimulation required cAMP-dependent protein kinase activity. Thus, transcriptional regulation of the SH2D2A gene in activated T cells is critically dependent on a CRE in the proximal promoter region.
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Øynebråten, Inger; Oynebraten, Inger; Bakke, Oddmund; Brandtzæg, Per; Johansen, Finn Erik & Haraldsen, Guttorm
(2004).
Rapid chemokine secretion from endothelial cells originates from 2 distinct compartments.
Blood.
ISSN 0006-4971.
104(2),
p. 314–320.
Show summary
The neutrophil-attracting chemokine interleukin 8 (IL-8) is stored in the Weibel-Palade body (WPB) of endothelial cells (ECs) from which it can be rapidly released after exposure to the secretagogues histamine or thrombin. In this manner, IL-8 may enable rapid recruitment of leukocytes to inflammatory sites. To explore the possible storage of EC-derived chemokines that may attract other subsets of leukocytes, we examined the intracellular localization and secretagogue responsiveness of growth-related oncogene alpha (GROalpha), monocyte chemoattractant protein-1 (MCP-1), eotaxin-3, interferon-gamma-inducible protein 10 (IP-10), and regulated on activation, normal T-cell expressed and secreted (RANTES). While eotaxin-3, GROalpha, and MCP-1 were rapidly released from ECs, the release of the T-cell attractors RANTES and IP-10 was not sensitive to the secretagogues. Moreover, of the 3 former chemokines, only eotaxin-3 was stored in WPBs. GROalpha and MCP-1 resided mainly in smaller vesicles compatible with sorting to a different, histamine-responsive compartment, which has been described in ECs although not reported to contain chemokines. In conclusion, we propose that rapid release of chemokines is restricted to those primarily recruiting leukocytes of the innate immune system, and that their storage in ECs is not restricted to the WPB compartment.
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Brandtzæg, Per; Johansen, Finn Eirik; Bækkevold, Espen S.; Carlsen, Hege Synnøve & Farstad, Inger Nina
(2004).
The traffic of mucosal lymphocytes to extraintestinal sites.
Journal of Pediatric Gastroenterology and Nutrition - JPGN.
ISSN 0277-2116.
39,
p. S725–S726.
-
Farkas, Lorant; Kvale, Espen Østhagen; Johansen, Finn Eirik; Jahnsen, Frode Lars & Lund-Johansen, F
(2004).
Plasmacytoid dendritic cells activate allergen-specific Th2 memory cells: modulation by CpG oligodeoxynucleotides.
Journal of Allergy and Clinical Immunology.
ISSN 0091-6749.
114,
p. 436–443.
-
Elm, C; Braathen, Ranveig; Bergmann, S; Frank, R; Vaerman, JP & Kaetzel, CS
[Show all 9 contributors for this article]
(2004).
Ectodomains 3 and 4 of human polymeric immunoglobulin receptor (hpIgR) mediate invasion of Streptococcus pneumoniae into the epithelium.
Journal of Biological Chemistry.
ISSN 0021-9258.
279,
p. 6296–6304.
-
Claypool, SM; Dickinson, BL; Wagner, JS; Johansen, Finn Eirik; Venu, N & Borawski, JA
[Show all 8 contributors for this article]
(2004).
Bidirectional transepithelial IgG transport by a strongly polarized basolateral membrane Fc gamma-receptor.
Molecular and Cellular Biology.
ISSN 0270-7306.
15,
p. 1746–1759.
-
Johansen, Finn Eirik & Brandtzæg, Per
(2004).
Transcriptional regulation of the mucosal IgA system.
Trends in immunology.
ISSN 1471-4906.
25,
p. 150–157.
-
Schjerven, Hilde; Tran, Thien Ngoc; Brandtzæg, Per & Johansen, Finn Eirik
(2004).
De novo synthesized RelB mediates TNF-induced up-regulation of the human polymeric Ig receptor.
Journal of Immunology.
ISSN 0022-1767.
173,
p. 1849–1857.
-
Sun, K; Johansen, Finn Eirik; Eckmann, L & Metzger, DW
(2004).
An important role for polymeric Ig receptor-mediated transport of IgA in protection against Streptococcus pneumoniae nasopharyngeal carriage.
Journal of Immunology.
ISSN 0022-1767.
173,
p. 4576–4581.
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Schjerven, Hilde; Brandtzæg, Per & Johansen, Finn Eirik
(2003).
Hepatocyte NF-1 and STAT6 cooperate with additional DNA-binding factors to activate transcription of the human polymeric Ig receptor gene in response to IL-4.
Journal of Immunology.
ISSN 0022-1767.
170(12),
p. 6048–6056.
-
Bækkevold, Espen S.; Roussigné, M; Yamanaka, Takeshi; Johansen, Finn Eirik; Jahnsen, Frode Lars & Amalric, F
[Show all 10 contributors for this article]
(2003).
Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules.
American Journal of Pathology.
ISSN 0002-9440.
163,
p. 69–79.
-
Uren, TK; Johansen, Finn Eirik; Wijburg, OLC; Koentgen, F; Brandtzæg, Per & Strugnell, RA
(2003).
Role of the polymeric Ig receptor in mucosal B cell homeostasis.
Journal of Immunology.
ISSN 0022-1767.
170,
p. 2531–2539.
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Braathen, Ranveig; Sørensen, Vigdis; Brandtzæg, Per; Sandlie, Inger & Johansen, Finn Eirik
(2002).
The carboxyl-terminal domains of IgA and IgM direct isotype-specific polymerization and interaction with the polymeric immunoglobulin receptor.
Journal of Biological Chemistry.
ISSN 0021-9258.
277(45),
p. 42755–42762.
Full text in Research Archive
Show summary
Mucosal surfaces are protected by polymeric immunoglobulins that are transported across the epithelium by the polymeric immunoglobulin receptor (pIgR). Only polymeric IgA and IgM containing a small polypeptide called the "joining" (J) chain can bind to the pIgR. J chain-positive IgA consists of dimers, and some larger polymers, whereas only IgM pentamers incorporate the J chain. We made domain-swap chimeras between human IgA1 and IgM and found that the COOH-terminal domains of the heavy chains (Ca3 and Cm4, respectively) dictated the size of the polymers formed and also which polymers incorporated the J chain. We also showed that chimeric IgM molecules engineered to contain Ca3 were able to bind the rabbit pIgR. Since the rabbit pIgR normally does not bind IgM, these results suggest that the COOH-terminal domain of the polymeric immunoglobulins is primarily responsible for interaction with the pIgR. Finally, we made a novel chimeric IgA immunoglobulin, containing the terminal domain from IgM. This recombinant molecule formed J chain-containing pentamers that could, like IgA, efficiently form covalent complexes with the human pIgR ectodomain, known as secretory component.
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Norderhaug, L.; Johansen, Finn Eirik & Sandlie, Inger
(2002).
BALANCED EXPRESSION OF SINGLE SUBUNITS IN A MULTISUBUNIT PROTEIN, ACHIEVED BY CELL FUSION OF INDIVIDUAL TRANSFECTANTS.
European Journal of Biochemistry (EJB).
ISSN 0014-2956.
269(13),
p. 3205–3210.
-
Carlsen, Hege Synnøve; Bækkevold, Espen S.; Johansen, Finn Eirik; Haraldsen, Guttorm & Brandtzæg, Per
(2002).
B cell attracting chemokine 1 (CXCL13) and its receptor CXCR5 are expressed in normal and aberrant gut associated lymphoid tissue.
Gut.
ISSN 0017-5749.
51,
p. 364–371.
-
Farstad, Inger Nina; Johansen, Finn Eirik; Vlatkovic, L.; Jahnsen, Jørgen; Scott, Helge & Fausa, Olav
[Show all 9 contributors for this article]
(2002).
Heterogeneity of intraepithelial lymphocytes in refractory sprue: potential implications of CD30 expression.
Gut.
ISSN 0017-5749.
51,
p. 372–378.
-
Olaussen, Richard Willfred; Johansen, Finn Eirik; Lundin, Knut E. A.; Jahnsen, Jørgen; Brandtzæg, Per & Farstad, Inger Nina
(2002).
Interferon-gamma-secreting T cells localize to the epithelium in coeliac disease.
Scandinavian Journal of Immunology.
ISSN 0300-9475.
56,
p. 652–664.
-
Nilsen, Ellen M.; Johansen, Finn Eirik & Brandtzæg, Per
(2001).
Quantitative PCR for measurement of cytokine expression. In: Interleukin Protocols (Eds.: O'Neill L, Bowie A).
In Walker, J.M. (Eds.),
Methods in Molecular Medicine.
Humana Press, Totowa, NJ.
p. 59–76.
-
Schjerven, Hilde; Brandtzæg, Per & Johansen, Finn Eirik
(2001).
A novel NF-kappaB/Rel site in intron 1 cooperates with proximal promoter elements to mediate TNF-alfa-induced transcription of the human polymeric Ig receptor.
Journal of Immunology.
ISSN 0022-1767.
167,
p. 6412–6420.
Show summary
Secretory Abs constitute the first line of specific immune defense at mucosal surfaces. Such Abs are generated by the active transport of polymeric Ig (pIg) across secretory epithelia mediated by the pIg receptor (pIgR), also known as transmembrane secretory component (SC). The pro-inflammatory cytokine TNF-alfa is a key mediator of host responses to infections, and it can stimulate protein synthesis-dependent transcriptional up-regulation of pIgR/SC in the HT-29 intestinal adenocarcinoma cell line. By reporter gene assay we identified a novel TNF-alfa-responsive region located within a 748-bp fragment in intron 1 of the human pIgR/SC gene which depended on an NF-kappaB/Rel site for full responsiveness. In vitro binding studies (EMSA) demonstrated preferential binding of the NF-kappaB/Rel family member p65 (RelA) to this DNA element after TNF-alfa stimulation, with weaker and more delayed binding of p50. Furthermore, the TNF-alfa-responsive region in intron 1 required cooperation with DNA elements located in the proximal promoter region of the gene. Mutational analysis demonstrated that an ISRE near the transcriptional start site in exon 1 was involved in the TNF-alfa responsiveness. Thus, DNA elements located more than 4 kb apart were found to cooperate in TNF-alfa-induced pIgR/SC up-regulation. The intronic TNF-alfa-responsive enhancer overlapped with a recently identified IL-4-responsive enhancer. Several intronic DNA elements found to be functionally important in the human gene are highly conserved between the human and mouse pIgR/SC genes, suggesting the presence of a conserved cytokine-responsive enhancer region.
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Johansen, Finn Eirik; Braathen, Ranveig & Brandtzæg, Per
(2001).
The J chain is essential for polymeric Ig receptor-mediated epithelial transport of IgA.
Journal of Immunology.
ISSN 0022-1767.
167,
p. 5185–5192.
Show summary
Local production of secretory (S)IgA provides adaptive immunologic protection of mucosal surfaces, but SIgA is also protective when
administered passively, such as in breast milk. Therefore, SIgA is a potential candidate for therapeutic administration, but its complex
structure with four different polypeptide chains produced by two distinct cell types complicates recombinant production. The J chain is
critical in the structure of SIgA because it is required for efficient polymerization of IgA and for the affinity of such polymers to the
secretory component (SC)/polymeric (p)IgR. To better understand the role of the J chain in SIgA production, we have generated various
mutant forms of the human J chain and analyzed the function of these mutants when coexpressed with IgA. We found that the C terminus of the J chain was not required for the formation of IgA polymers, but was essential for the binding of pIgA to SC. Likewise, we found that two of the intrachain disulfide bridges (Cys13:Cys101 and Cys109:Cys134) were also required for the binding of pIgA to SC but, interestingly, not for IgA polymerization. Conversely, the last intrachain disulfide bridge (Cys72:Cys92) was not essential for either of these two J chain functions. Finally, we demonstrated that the presence of only Cys15 or Cys69 was sufficient to support polymerization of IgA, but that these polymers were mostly noncovalently stabilized. Nevertheless, these polymers bound free SC with nearly the same affinity as pIgA containing wild-type J chain, but were transcytosed by pIgR-expressing polarized epithelial cells at a reduced efficiency.
-
Brandtzæg, Per & Johansen, Finn Eirik
(2001).
Confusion about the polymeric Ig receptor.
Trends in immunology.
ISSN 1471-4906.
22,
p. 545–546.
-
Nilsen, Ellen M.; Johansen, Finn Eirik & Brandtzæg, Per
(2000).
Measurements of cytokine mRNA expression by quantitative polymerase chain reaction in studies of celiac disease.
In Marsh, Michael N. (Eds.),
Celiac Disease. Methods and Protocols.
Humana Press, Totawa.
ISSN 0-89603-650-2.
p. 185–202.
-
Schjerven, Hilde; Johansen, Finn Eirik & Brandtzæg, Per
(2000).
Mechanism of IL-4-Mediated Up-Regulation of the Polymeric Ig Receptor: Role of STAT6 in Cell Type-Specific Delayed Transcriptional Response.
Journal of Immunology.
ISSN 0022-1767.
165,
p. 3898–3906.
Show summary
Abstract
The polymeric immunoglobulin receptor (pIgR) mediates transport of dimeric immunoglobulin (Ig)A and pentameric IgM across mucosal epithelia, thereby generating secretory antibodies. Its expression is upregulated at the transcriptional level by interleukin (IL)-4 in HT-29 cells. Here, we demonstrate that IL-4 mediates upregulation of human pIgR through a 554-bp IL-4-responsive enhancer in intron 1. Mutation of a binding site for signal transducer and activator of transcription (STAT)-6 within this region abolished IL-4-induced enhancement, while an adjacent putative C/EBP site was dispensable. IL-4 treatment induced binding of STAT6 to the intronic STAT6 site, but cooperation with nearby upstream and downstream DNA elements was required for IL-4 responsiveness. Furthermore, IL-4-mediated increased transcription of the pIgR-derived enhancer, like the endogenous pIgR gene, required de novo protein synthesis. Interestingly, a conditionally active form of STAT6 sufficed to activate a pIgR-derived enhancer in HT-29 cells but not in Cos-1 cells, suggesting a requirement for cell type-specific factors. Thus, STAT6 activation mediates a delayed transcriptional enhancement of pIgR by induction of a de novo synthesized protein that cooperates with STAT6 itself bound to its cognate DNA element in intron 1. This mechanism may represent a general strategy for how pleiotropic cytokines elicit cell type-specific transcriptional responses.
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Johansen, Finn Eirik; Braathen, Ranveig & Brandtzæg, Per
(2000).
Role of J chain in secretory immunoglobulin formation.
Scandinavian Journal of Immunology.
ISSN 0300-9475.
52(3),
p. 240–248.
Show summary
The joining (J) chain is a small polypeptide, expressed by mucosal and glandular plasma cells, which regulates polymer formation of IgA and IgM. J-chain incorporation into polymeric IgA (pIgA, mainly dimers) and pentameric IgM endows these antibodies with several salient features: a high valency of antigen-binding sites, which make them suitable for agglutinating bacteria and viruses; little or no complement-activating potential, which allow them operate in a non-inflammatory fashion; and, most importantly, only J-chain-containing polymers show high affinity for the polymeric Ig receptor (pIgR), also known as transmembrane secretory component (SC). This epithelial glycoprotein mediates active external transfer of pIgA and pentameric IgM to exocrine secretions. Thus, secretory IgA (SIgA) and SIgM, as well as free SC, are generated by endoproteolytic cleavage of the pIgR extracellular domain. The secretory antibodies form the "first line" of defense against pathogens and noxious substances that favor the mucosae as their portal of entry. The J chain is involved in creating the binding site for pIgR/SC in the Ig polymers not only by determining the polymeric quaternary structure, but apparently also by interacting directly with the receptor protein. Therefore, both the J chain and the pIgR/SC are key proteins in secretory immunity.
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Jahnsen, Frode Lars; Haye, Rolf; Gran, Einar; Brandtzæg, Per & Johansen, Finn Eirik
(1999).
Glucocorticosteroids Inhibit mRNA Expression for Eotaxin, Eotaxin-2, and Monocyte-Chemotactic Protein-4 in Human Airway Inflammation with Eosinophilia.
Journal of Immunology.
ISSN 0022-1767.
163,
p. 1545–1551.
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Johansen, Finn Eirik; Norderhaug, Inger Natvig; Roe, M.; Sandlie, Inger & Brandtzæg, Per
(1999).
Recombinant expression of polymeric IgA: incorporation of J cahin and secretory component of human origin.
European Journal of Immunology.
ISSN 0014-2980.
29,
p. 1701–1708.
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Bækkevold, Espen S.; Jahnsen, Frode Lars; Johansen, Finn Eirik; Bakke, Oddmund; Gaudernack, Gustav & Brandtzæg, Per
[Show all 7 contributors for this article]
(1999).
Culture characterization of differentiated high endothelial venule cells from human tonsils.
Laboratory Investigation.
ISSN 0023-6837.
79(3),
p. 327–336.
Show summary
High endothelial venules (HEV) are specialized vessels that support abundant lymphocyte emigration from peripheral blood into secondary lymphoid organs. HEV endothelial cells (HEVEC) exhibit particular structural and functional features, including secretion of the HEV-specific extracellular matrix protein hevin and an array of uniquely glycosylated counter-receptors for L-selectin expressed on lymphocytes. These ligands are collectively called the peripheral lymph node addressin (PNAd), originally defined by the monoclonal antibody MECA-79. PNAd expression was used to purify HEVEC by positive immunoselection from enzyme-digested human tonsils after negative immunoselection for other cells. Purified HEVEC maintained secretion of hevin and homogenous expression of intercellular adhesion molecule (ICAM)-1 (CD54), ICAM-2 (CD102), and CD31, at high levels following 8 days in culture. Expression of functional PNAd was maintained during the first 4 to 5 days of culture but decreased gradually and disappeared on day 8, while the expression of CD34 remained strong. However, the CD34 glycoform shifted toward the in situ phenotype of flat-walled vessels, suggesting that the observed loss of L-selectin binding determinants and MECA-79 antigen was due to down-regulation of the glycosyl- and sulfo-transferases essential for their expression. Our rapid and reproducible method to establish HEVEC cultures provides a useful mechanistic tool for identification of the factors that induce and maintain the HEV phenotype, as well as a source for isolation of HEV-specific genes.
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Norderhaug, Inger Natvig; Johansen, Finn Eirik; Schjerven, Hilde & Brandtzæg, Per
(1999).
Regulation of the formation and external transport of secretory immunoglobulins.
Critical Reviews in Immunology.
ISSN 1040-8401.
19,
p. 481–508.
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Johansen, Finn Eirik; Pekna, Marcela; Norderhaug, Inger Natvig; Haneberg, Bjørn; Hietala, Max Albert & Krajci, Peter
[Show all 8 contributors for this article]
(1999).
Absence of epithelial immunoglobulin A transport, with increased mucosal leakiness, in polymeric immunoglobulin receptor/secretory component-deficient mice.
Journal of Experimental Medicine (JEM).
ISSN 0022-1007.
190,
p. 915–921.
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Brandtzæg, Per; Johansen, Finn Eirik; Krajci, Peter & Natvig, Inger Backer
(1998).
Human secretory component (the polymeric Ig receptor).
In Roitt, IM & Delves, J (Ed.),
Encyclopedia of Immunology, 2nd Ed.
Academic Press, London..
p. 2152–2158.