IL-22 Down-Regulates Cx43 Expression and Decreases Gap Junctional Intercellular Communication by Activating the JNK Pathway in Psoriasis

The Journal of Investigative Dermatology
Jingyao LiangXibao Zhang

Abstract

The roles of IL-22 in the pathomechanisms of psoriasis have been well demonstrated. Gap junctional intercellular communication (GJIC) is widely known for its involvement in multiple biological and pathological processes such as growth-related events, cell differentiation, and inflammation. Here, we show that IL-22 significantly decreased GJIC and down-regulated Cx43 expression in HaCaT cells. Cx43 overexpression markedly inhibited the proliferation of and increased GJIC in HaCaT cells, but the silencing of Cx43 exerted the opposite effects. Additionally, Cx43 overexpression effectively rescued the IL-22-induced decrease in GJIC in HaCaT cells. The IL-22-induced down-regulation of Cx43 expression and decrease in GJIC can be significantly blocked by the JNK inhibitor SP600125 and by the overexpression of IL-22RA2 (which specifically binds to IL-22 and inhibits its activity), but not by the NF-κB inhibitor BAY11-7082, in HaCaT cells. Furthermore, the IL-22-induced down-regulation of Cx43 expression mediated by the JNK signaling pathway was confirmed in a mouse model of IL-22-induced psoriasis-like dermatitis. Similarly, Cx43 expression was significantly lower in the lesional skin than in the nonlesional skin of patients with psori...Continue Reading

Citations

Jul 31, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Canlong MoKun Wei
Sep 29, 2019·World Journal of Gastroenterology : WJG·Huan LiXiao-Ming Liu
Jul 8, 2020·International Journal of Molecular Sciences·María F Rozas-VillanuevaMauricio A Retamal
Apr 8, 2020·Cells·Manel B HammoudaJennifer Y Zhang
Aug 18, 2020·Journal of Ethnopharmacology·Kuei-Hung LaiTsong-Long Hwang
Jul 3, 2021·International Journal of Molecular Sciences·Erin M O'ShaughnessyPatricia E Martin
Nov 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ivanka K KoychevaMilen I Georgiev

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