Inger Johanne Schytte Blix

• Balta, Maria; Schreurs, Olaf Joseph Franciscus; Blix, Inger Johanne Schytte & Schenck, Karl (2024). The effect of resolvin D1<inf>n-3 DPA</inf> on primary oral epithelial cell migration in vitro. European Journal of Oral Sciences. ISSN 0909-8836. doi: 10.1111/eos.12981.
• Balta, Maria G.; Schreurs, Olaf Joseph Franciscus; Halder, Rashi; Küntziger, Thomas M.; Sætre, Frank Ove & Blix, Inger Johanne Schytte [Vis alle 9 forfattere av denne artikkelen] (2022). RvD1n-3 DPA Downregulates the Transcription of Pro-Inflammatory Genes in Oral Epithelial Cells and Reverses Nuclear Translocation of Transcription Factor p65 after TNF-α Stimulation. International Journal of Molecular Sciences. ISSN 1661-6596. 23(23), s. 1–11. doi: 10.3390/ijms232314878. Fulltekst i vitenarkiv Vis sammendrag

  Specialized pro-resolving mediators (SPMs) are multifunctional lipid mediators that participate in the resolution of inflammation. We have recently described that oral epithelial cells (OECs) express receptors of the SPM resolvin RvD1n-3 DPA and that cultured OECs respond to RvD1n-3 DPA addition by intracellular calcium release, nuclear receptor translocation and transcription of genes coding for antimicrobial peptides. The aim of the present study was to assess the functional outcome of RvD1n-3 DPA–signaling in OECs under inflammatory conditions. To this end, we performed transcriptomic analyses of TNF-a-stimulated cells that were subsequently treated with RvD1n-3 DPA and found significant downregulation of pro-inflammatory nuclear factor kappa B (NF-kB) target genes. Further bioinformatics analyses showed that RvD1n-3 DPA inhibited the expression of several genes involved in the NF-kB activation pathway. Confocal microscopy revealed that addition of RvD1n-3 DPA to OECs reversed TNF-a-induced nuclear translocation of NF-kB p65. Co-treatment of the cells with the exportin 1 inhibitor leptomycin B indicated that RvD1n-3 DPA increases nuclear export of p65. Taken together, our observations suggest that SPMs also have the potential to be used as a therapeutic aid when inflammation is established.

• Balta, Maria; Schreurs, Olaf Joseph Franciscus; Hansen, Trond Vidar; Tungen, Jørn Eivind; Vik, Anders & Glaab, Enrico [Vis alle 10 forfattere av denne artikkelen] (2022). Expression and function of resolvin RvD1n-3 DPA receptors in oral epithelial cells. European Journal of Oral Sciences. ISSN 0909-8836. 130:e12883(4), s. 1–10. doi: 10.1111/eos.12883. Fulltekst i vitenarkiv
• Solhaug, Maren Bråten; Schreurs, Olaf Joseph Franciscus; Schenck, Karl; Blix, Inger Johanne Schytte & Bækkevold, Espen Sønderaal (2021). Origin of langerin (CD207)-expressing antigen presenting cells in the normal oral mucosa and in oral lichen planus lesions. European Journal of Oral Sciences. ISSN 0909-8836. 130:e12835(1), s. 1–12. doi: 10.1111/eos.12835. Fulltekst i vitenarkiv
• Balta, Maria; Papathanasiou, Evangelos; Blix, Inger Johanne S. & Van Dyke, T E (2021). Host Modulation and Treatment of Periodontal Disease. Journal of Dental Research. ISSN 0022-0345. 100, s. 798–809. doi: 10.1177/0022034521995157.
• 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.

• 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.

• Thorlakson, Hong Huynh; Schreurs, Olaf Joseph Franciscus; Schenck, Karl & Blix, Inger Johanne S. (2016). Lysophosphatidic acid regulates adhesion molecules and enhances migration of human oral keratinocytes. . European Journal of Oral Sciences. ISSN 0909-8836. 124(2), s. 164–171. doi: 10.1111/eos.12255.
• Bjerkan, Louise; Schreurs, Olav Joseph F; Engen, Stian André; Jahnsen, Frode Lars; Bækkevold, Espen Sønderaal & Blix, Inger Johanne S. [Vis alle 7 forfattere av denne artikkelen] (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 [Vis alle 8 forfattere av denne artikkelen] (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
• Huynh-Torlakovic, Hong; Bjerkan, Louise; Schenck, Karl & Blix, Inger Johanne S. (2012). Distribution of carcinoembryonic antigen-related cellular adhesion molecules in human gingiva. European Journal of Oral Sciences. ISSN 0909-8836. 120(5), s. 395–401. doi: 10.1111/j.1600-0722.2012.00981.x. Vis sammendrag

  Carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs) are glycoproteins produced in epithelial, endothelial, lymphoid, and myeloid cells. Carcinoembryonic antigen-related cellular adhesion molecules mediate cell-cell contact and host-pathogen interactions. The aims of this study were to map the distribution and examine the regulation of CEACAMs in human gingival sites. Quantitative real-time PCR performed on human gingival biopsies from periodontitis sites revealed mRNA coding for CEACAM1, -5, -6, and -7. Immunohistochemistry showed that CEACAMs were not found in oral gingival epithelium, except for CEACAM5 in periodontitis. Carcinoembryonic antigen-related cellular adhesion molecules 1, 5, and 6 were present in the oral sulcular epithelium of periodontitis but not in that of healthy gingiva. In junctional epithelium, all three molecules were present in healthy gingiva, but in periodontitis only CEACAM1 and -6 were detected. Staining for CEACAM1 and -6 was also seen in the inflammatory cell infiltrate in periodontitis. No staining for CEACAM7 was found. Proinflammatory mediators, including lipopolysaccharide (LPS), tumour necrosis factor-α (TNF-α)/interleukin-1β (IL-1β), and interferon-γ (IFN-γ), increased the expression of CEACAM1 and CEACAM6 mRNAs in cultured human oral keratinocytes. CEACAM1 and CEACAM6 mRNAs were also strongly up-regulated upon stimulation with lysophosphatidic acid. In conclusion, the distribution of different CEACAMs was related to specific sites in the gingiva. This might reflect different functional roles in this tissue.

• Blix, Inger Johanne S.; Helgeland, Kristen; Kähler, Hanne & Lyberg, Torstein (1999). LPS from Actinobacillus actinomycetemcomitans and the expression of beta2 integrins and L-selectin in an ex vivo human whole blood system. European Journal of Oral Sciences. ISSN 0909-8836. 107(1), s. 14–20.
• Blix, Inger Johanne S.; Helgeland, Kristen; Hvattum, Erlend & Lyberg, Torstein (1999). Lipopolysaccharide from Actinobacillus actinomycetemcomitans stimulates production of interleukin-1ß, tumor necrosis factor-a, interleukin-6, and interleukin-1 receptor antagonist in human whole blood. Journal of Periodontal Research. ISSN 0022-3484. 34.
• Blix, Inger Johanne S. & Helgeland, Kristen (1998). LPS from Actinobacillus actinomycetemcomitans and production of nitric oxide in murine macrophages J774. European Journal of Oral Sciences. ISSN 0909-8836. 106, s. 576–581.
• Blix, Inger Johanne S.; Helgeland, Kristen; Hvattum, Erlend & Lyberg, Torstein (1998). Lipopolysaccharide from Actinobacillus actinomycetemcomitans stimulates production of interleukin-1. European Journal of Oral Sciences. ISSN 0909-8836. 106.
• Blix, Inger Johanne S.; Hars, Renate; Preus, Hans Ragnar & Helgeland, Kristen (1992). Entrance of Actinobacillus actinomycetemcomitans into HEp-2 cells in vitro. Journal of Periodontology. ISSN 0022-3492. 63, s. 723–728.
• Blix, Inger Johanne S.; Preus, Hans Ragnar & Olsen, Ingar (1990). Invasive growth of Actinobacillus actinomycetemcomitans on solid medium (TSBV). Acta Odontologica Scandinavica. ISSN 0001-6357. 48, s. 313–318.

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• Stian André, Engen; Schreurs, Olaf Joseph Franciscus; Fernanda, Petersen; Blix, Inger Johanne S.; Espen S., Bækkevold & Schenck, Karl (2018). The regulatory role of the oral commensal Streptococcus mitis on human monocytes.
• Rørvik, Gro Herredsvela; Schreurs, Olaf Joseph Franciscus; Engen, Stian; Blix, Inger Johanne S.; Petersen, Fernanda Cristina & Schenck, Karl (2017). Antibody reactivity to the oral commensal Streptococcus mitis in serum and saliva.
• Engen, Stian; Schreurs, Olaf Joseph Franciscus; Petersen, Fernanda Cristina; Blix, Inger Johanne S.; Bækkevold, Espen Sønderaal & Schenck, Karl (2017). Regulation of human monocytes by the oral commensal Streptococcus mitis: a role for PGE2?
• 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 [Vis alle 8 forfattere av denne artikkelen] (2015). The oral commensal Streptococcus mitis shows a mixed memory Th cell signature that is similar to and cross-reactive with Streptococcus pneumoniae.
• Blix, IJS; Preus, Hans Ragnar; Helgeland, Kristen & Olsen, Ingar (1988). Invasive growth of Aa in vitro of an oral mucosal equivalent. Journal of Dental Research. ISSN 0022-0345. 67(78).
• Preus, Hans Ragnar; Blix, IJS & Olsen, Ingar (1988). DNA fingerprinting vs. phenotypic expression of 10 wild strains of Aa. Journal of Dental Research. ISSN 0022-0345. 67(77).
• Blix, Inger johanne schytte (1999). Actinobacillus actinomycetemcomitans. Invasion and inflammatory mediators. Universitetet i Oslo. ISSN 82-91757-07-0.

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