Received: AugAccepted: OctoPublished: November 4, 2021Ĭopyright: © 2021 Naruke et al. PLoS ONE 16(11):Įditor: Chuen-Mao Yang, Chang Gung University, TAIWAN (2021) Tpl2 contributes to IL-1β-induced IL-8 expression via ERK1/2 activation in canine dermal fibroblasts. Taken together, our data indicate the importance of Tpl2 in the modulation of ERK1/2 signaling involved in the IL-1β-induced development of autoimmune diseases affecting the dermal tissue, such as atopic dermatitis.Ĭitation: Naruke A, Nakano R, Nunomura J, Suwabe Y, Nakano M, Namba S, et al. We confirmed that the silencing of Tpl2 in siRNA-transfected fibroblasts prevented both in IL-1β-induced IL-8 expression and ERK1/2 phosphorylation. Notably, a Tpl2 inhibitor reduced IL-1β-induced IL-8 expression and ERK1/2 phosphorylation. IL-1β failed to induce IL-8 expression in cells transfected with siRNA for ERK1, or ERK2. IL-1β induced ERK1/2 phosphorylation, which was attenuated in the presence of an ERK1/2 inhibitor. ERK1/2 inhibitors significantly reduced IL-1β-induced IL-8 expression, whereas the inhibitor for p38 MAPK or JNK had no effect. We observed an increase in the expression of IL-8 mRNA and protein in cells treated with IL-1β. We also identified that a MAP3K Tpl2 acts as an upstream modulator of IL-1β-induced ERK1/2 activation in dermal fibroblasts. To elucidate the mechanism of the onset of autoimmune diseases, we established a model for IL-1β-induced dermatitis and investigated MAPK signaling pathways in IL-1β-induced IL-8 expression. IL-1β-mediated induction of IL-8 expression is important for the pathogenesis of autoimmune diseases however, the intracellular singling remains to be understood. IL-8 induces the activation and recruitment of innate immune cells such as neutrophils to the site of inflammation. The pro-inflammatory cytokine interleukin 1β (IL-1β) induces the expression of chemokines, such as interleukin 8 (IL-8), in autoimmune diseases of the skin. dermal fibroblasts) in autoimmune diseases of the skin, such as atopic dermatitis, has been obscure. However, the contribution of sentinel immune cells (i.e. In autoimmune diseases, fibroblasts produce and secrete various cytokines and act as sentinel immune cells during inflammatory states.
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