title: Interferon Regulatory Factor 6 Promotes Keratinocyte Differentiation in Response to Porphyromonas gingivalis.
abstract: We recently demonstrated that the expression of the interferon regulatory factor 6 (IRF6) transcription factor in oral keratinocytes was stimulated by the periodontal pathogenPorphyromonas gingivalisHere, we have established that IRF6 promotes the differentiation of oral keratinocytes in response toP. gingivalisThis was evidenced by the IRF6-dependent upregulation of specific markers of keratinocyte terminal differentiation (e.g., involucrin [IVL] and keratin 13 [KRT13]), together with additional transcriptional regulators of keratinocyte differentiation, including Grainyhead-like 3 (GRHL3) and Ovo-like zinc finger 1 (OVOL1). We have previously established that the transactivator function of IRF6 is activated by receptor-interacting protein kinase 4 (RIPK4). Consistently, the silencing of RIPK4 inhibited the stimulation of IVL, KRT13, GRHL3, and OVOL1 gene expression. IRF6 was shown to also regulate the stimulation of transglutaminase-1 (TGM1) gene expression byP. gingivalis, as well as that of small proline-rich proteins (e.g., SPRR1), which are covalently cross-linked by TGM1 to other proteins, including IVL, during cornification. The expression of the tight junction protein occludin (OCLN) was found to also be upregulated in an IRF6-dependent manner. IRF6 was demonstrated to be important for the barrier function of oral keratinocytes; specifically, silencing of IRF6 increasedP. gingivalis-induced intercellular permeability and cell invasion. Taken together, our findings potentially position IRF6 as an important mediator of barrier defense againstP. gingivalis.
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Huynh
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria, Australia.
authors.forename: Glen M
authors.initials: GM
authors.lastname: Scholz
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria, Australia.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Aw
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria, Australia e.reynolds@unimelb.edu.au.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Reynolds
mesh_terms: D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D002460:Cell Line; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D015603:Keratinocytes / Q000502:physiology*; D016966:Porphyromonas gingivalis / Q000254:growth & development*
chemical_list: D015415:Biomarkers; C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors
keywords: GRHL3; IRF6; Porphyromonas gingivalis; RIPK4; barrier function; differentiation; keratinocyte