Interferon regulatory Factor 6 promotes Keratinocyte differentiation in response to Porphyromonas gingivalis Academic Article uri icon

abstract

  • ABSTRACT We recently demonstrated that the expression of the interferon regulatory factor 6 (IRF6) transcription factor in oral keratinocytes was stimulated by the periodontal pathogen Porphyromonas gingivalis . Here, we have established that IRF6 promotes the differentiation of oral keratinocytes in response to P. gingivalis . This 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 by P. 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 increased P. gingivalis -induced intercellular permeability and cell invasion. Taken together, our findings potentially position IRF6 as an important mediator of barrier defense against P. gingivalis .

publication date

  • 2017