MEK-ERK signaling diametrically controls the stimulation of IL-23p19 and EBI3 expression in epithelial cells by IL-36γ

Immunology and Cell Biology
Glen M ScholzEric C Reynolds

Abstract

Interleukin (IL)-36 cytokines are important regulators of mucosal homeostasis and inflammation. We previously established that oral epithelial cells strongly upregulate IL-36γ expression in response to the bacterial pathogen Porphyromonas gingivalis. Here, we have established that IL-36γ stimulates the expression of the IL-12 cytokine family members, IL-23p19 and Epstein-Barr Virus-Induced Gene 3 (EBI3), by oral epithelial cells; their expression was also selectively stimulated by IL-36α. Notably, IL-23p19 and EBI3 expression was not stimulated by P. gingivalis, thus suggesting that their expression by the oral epithelium in response to P. gingivalis is likely to be mediated in an autocrine manner by IL-36γ. The IL-36γ-inducible expression of IL-23p19 and EBI3 was found to be diametrically regulated by the mitogen-activated protein kinase/extracellular signal regulated kinase (MEK)-extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, whereby the activation of MEK-ERK signaling likely functions as a negative feedback mechanism to limit EBI3 expression. Furthermore, epidermal growth factor receptor (EGFR) signaling, which is important for mucosal homeostasis, was demonstrated to modulate, in a MEK-ERK-dependent manner, the...Continue Reading

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Citations

Jun 20, 2018·Infection and Immunity·Glen M ScholzEric C Reynolds
Apr 30, 2020·Life Science Alliance·Jérémie D GoldsteinCem Gabay
Dec 24, 2019·Frontiers in Cell and Developmental Biology·Dawn QueenLiang Liu
Jan 22, 2020·Scientific Reports·Hidehiko FukushimaKazumitsu Sugiura
Dec 2, 2020·PloS One·Florence EcoeurChristine Guntermann
Jan 9, 2021·Immunopharmacology and Immunotoxicology·Yan LiMingcai Li
Mar 12, 2019·Cytokine·Jacqueline E HeathEric C Reynolds

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