Stian Engen

• Engen, Stian André; Rørvik, Gro Herredsvela; Schreurs, Olaf Joseph Franciscus; Blix, Inger Johanne S. & Schenck, Karl (2017). The oral commensal Streptococcus mitis activates the aryl hydrocarbon receptor in human oral epithelial cells. International Journal of Oral Science.  ISSN 1674-2818.  9(3), s 145- 150 . doi: 10.1038/ijos.2017.17 Fulltekst i vitenarkiv. Vis sammendrag

  Streptococcus mitis (S. mitis) is a pioneer commensal bacterial species colonizing many of the surfaces of the oral cavity in healthy individuals. Yet, not much information is available regarding its interaction with the host. We used examination of its transcriptional regulation in oral keratinocytes to elucidate some of its potential roles in the oral cavity. Transcription factor analysis of oral keratinocytes predicted S. mitis-mediated activation of aryl hydrocarbon receptor (AhR). Activation and functionality of AhR was confirmed through nuclear translocation determined by immunofluorescence microscopy and real-time polymerase chain reaction with reverse transcription analysis of CYP1A1, the hallmark gene for AhR activation. Addition of Streptococcus mutans or Streptococcus gordonii did not induce CYP1A1 transcription in the keratinocyte cultures. Introduction of an AhR-specific inhibitor revealed that S. mitis-mediated transcription of CXCL2 and CXCL8 was regulated by AhR. Elevated levels of prostaglandin E2 (enzyme-linked immunosorbent assay) in supernatants from S. mitis-treated oral epithelial cells were also attenuated by inhibition of AhR activity. The observed AhR-regulated activities point to a contribution of S. mitis in the regulation of inflammatory responses and thereby to wound healing in the oral cavity. The concept that the oral commensal microbiota can induce AhR activation is important, also in view of the role that AhR has in modulation of T-cell differentiation and as an anti-inflammatory factor in macrophages.

• Engen, Stian André; Schreurs, Olaf Joseph Franciscus; Petersen, Fernanda Cristina; Blix, Inger Johanne S.; Bækkevold, Espen Sønderaal & Schenck, Karl (2017). The Regulatory Role of the Oral Commensal Streptococcus mitis on Human Monocytes. Scandinavian Journal of Immunology.  ISSN 0300-9475.  87(2), s 80- 87 . doi: 10.1111/sji.12636
• Thorlakson, Hong Huynh; Engen, Stian André; Schreurs, Olaf Joseph Franciscus; Schenck, Karl & Blix, Inger Johanne S. (2017). Lysophophatidic acid induces expression of genes in human oral keratinocytes involved in wournd healing. Archives of Oral Biology.  ISSN 0003-9969.  80, s 153- 159 . doi: 10.1016/j.archoralbio.2017.04.008 Fulltekst i vitenarkiv. Vis sammendrag

  OBJECTIVE: Epithelial cells participate in wound healing by covering wounds, but also as important mediators of wound healing processes. Topical application of the phospholipid growth factor lysophosphatidic acid (LPA) accelerates dermal wound healing and we hypothesized that LPA can play a role in human oral wound healing through its effects on human oral keratinocytes (HOK). DESIGN: HOK were isolated from gingival biopsies and exposed to LPA. The LPA receptor profile, signal transduction pathways, gene expression and secretion of selected cytokines were analyzed. RESULTS: HOK expressed the receptors LPA1, LPA5 and LPA6 and LPA activated the ERK1/2, JNK and p38 intracellular pathways, substantiated by secretion of IL-6 and IL-8. The early (2h) and intermediate (6h) gene expression profiles of HOK after LPA treatment showed a wide array of regulated genes. The majority of the strongest upregulated genes were related to chemotaxis and inflammation, and became downregulated after 6h. At 6h, genes coding for factors involved in extracellular matrix remodeling and re-epithelialization became highly expressed. IL-36γ, not earlier known to be regulated by LPA, was strongly transcribed and translated but not secreted. CONCLUSIONS: After stimulation with LPA, HOK responded by regulating factors and genes that are essential in wound healing processes. As LPA is found in saliva and is released by activated cells after wounding, our results indicate that LPA has a favorable physiological role in oral wound healing. This may further point towards a beneficial role for application of LPA on oral surgical or chronic wounds.

• Rukke, Håkon Valen; Engen, Stian André; Schenck, Karl & Petersen, Fernanda Cristina (2016). Capsule expression in Streptococcus mitis modulates interaction with oral keratinocytes and alters susceptibility to human antimicrobial peptides. Molecular Oral Microbiology (MOM).  ISSN 2041-1006.  31(4), s 302- 313 . doi: 10.1111/omi.12123 Vis sammendrag

  Streptococcus mitis is a colonizer of the oral cavity and the nasopharynx, and is closely related to Streptococcus pneumoniae. Both species occur in encapsulated and unencapsulated forms, but in S. mitis the role of the capsule in host interactions is mostly unknown. Therefore, the aim of this study was to examine how capsule expression in S. mitis can modulate interactions with the host with relevance for colonization. The S. mitis type strain, as well as two mutants of the type strain, an isogenic capsule deletion mutant, and a capsule switch mutant expressing the serotype 4 capsule of S. pneumoniae TIGR4, were used. Wild-type and capsule deletion strains of S. pneumoniae TIGR4 were included for comparison. We found that capsule production in S. mitis reduced adhesion to oral and lung epithelial cells. Further, exposure of oral epithelial cells to encapsulated S. mitis resulted in higher interleukin-6 and CXCL-8 transcription levels relative to the unencapsulated mutant. Capsule expression in S. mitis increased the sensitivity to human neutrophil peptide 1-3 but reduced the sensitivity to human β-defensin-3 and cathelicidin. This was in contrast with S. pneumoniae in which capsule expression has been generally associated with increased sensitivity to human antimicrobial peptides (AMPs). Collectively, these findings indicate that capsule expression in S. mitis is important in modulating interactions with epithelial cells, and is associated with increased or reduced susceptibility to AMPs depending on the nature of the AMP.

• Bjerkan, Louise; Schreurs, Olav Joseph F; Engen, Stian André; Jahnsen, Frode Lars; Bækkevold, Espen Sønderaal; Blix, Inger Johanne S. & Schenck, Karl (2015). The short form of TSLP is constitutively translated in human keratinocytes and has characteristics of an antimicrobial peptide. Mucosal Immunology.  ISSN 1933-0219.  8(1), s 49- 56 . doi: 10.1038/mi.2014.41 Vis sammendrag

  Thymic stromal lymphopoietin (TSLP) has multifaceted immunological functions ranging from maintenance of tolerance to induction of disease. Two human transcript variants of TSLP are described: a long form (variant 1; lfTSLP) consisting of four exons and an alternative, short form (variant 2; sfTSLP) that lacks two exons compared with variant 1. SfTSLP has not been described at the protein level or functionally studied. Here, we demonstrate that the human sfTSLP is the predominant form of TSLP, constitutively expressed at the mRNA and protein level in keratinocytes of oral mucosa and skin and in salivary glands, is released in saliva, and is not regulated in the same manner as the long form. Compared with lfTSLP, sfTSLP exhibits a markedly stronger antibacterial activity. Synthetic sfTSLP did not activate signal transducer and activator of transcription 5 (STAT5) signaling in CD1c+ dendritic cells nor interfered with STAT5 activation by lfTSLP. SfTSLP may, therefore, act as an antimicrobial peptide in the oral cavity and on the skin to create a defense barrier that aids in the control of both commensal and pathogenic microbes. The results show that the two translational products of the TSLP gene have a different expression and different biological properties, and emphasize the importance of analyzing the two TSLP isoforms separately.

• Engen, Stian André; Rukke, Håkon Valen; Becattini, Simone; Jarrossay, David; Blix, Inger Johanne S.; Petersen, Fernanda Cristina; Sallusto, Federica & Schenck, Karl (2014). The Oral Commensal Streptococcus mitis Shows a Mixed Memory Th Cell Signature That Is Similar to and Cross-Reactive with Streptococcus pneumoniae. PLOS ONE.  ISSN 1932-6203.  9(8) . doi: 10.1371/journal.pone.0104306 Fulltekst i vitenarkiv.

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• Rørvik, Gro Herredsvela; Blix, Inger Johanne S.; Schenck, Karl & Engen, Stian André (2016). Activation of the aryl hydrocarbon receptor (AhR) and the induction of prostaglandin E2 (PGE2) in oral epithelial cells exposed to Streptococcus mitis.
• Engen, Stian André; Rukke, Håkon Valen; Becattini, Simone; Jarrossay, David; Blix, Inger Johanne S.; Petersen, Fernanda Cristina; Sallusto, Federica & Schenck, Karl (2015). The oral commensal Streptococcus mitis shows a mixed memory Th cell signature that is similar to and cross-reactive with Streptococcus pneumoniae..

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