Phospholipase C epsilon mediates cytokine cascade induced by acute disruption of epidermal permeability barrier in mice

Biochemistry and Biophysics Reports

Jiangmei Wu¹  Mengke Sun²  Shuchang Zhang²  Maoqiang Man²  Junkai Huang²  Lizhi Hu³  Jing Zhang⁴ 

[1] Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China;Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China;Dermatology Services, University of California San Francisco, San Francisco, CA, 94121, USA;Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin, 300070, China;

关键词: IL-22;    PLCε;    Skin inflammation;    Barrier function;    Psoriasis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Disruption of epidermal barrier is an important trigger in abnormal cutaneous inflammation. Phospholipase C epsilon (PLCε), a Ras/Rap1 effector, is essential for regulating cytokines production in different types of skin inflammation. Our previous studies have demonstrated that elevated expression of PLCε participates in the psoriasis-like inflammation in PLCε overexpressing transgenic mice model, while the reduction in PLCε expression attenuates inflammatory responses in either TPA- or DNFB-induced cutaneous inflammation. Here, we determined the role of PLCε in cutaneous inflammation induced by acute abrogation of epidermal permeability barrier. In comparison to wild type controls, PLCε KO mice exhibited reduced ear swelling and infiltration of granulocytes after tape-stripping. Moreover, expression levels of pro-inflammatory cytokines (IL-1α, IL-1β), chemokines (CXCL-1, CXCL-2, CCL20), and antimicrobial peptides (S100 proteins, MBD3) were lower in PLCε-deficient versus wild type mice. Likewise, expression levels of cytokines and chemokines were also lower in PLCε deficient keratinocytes and fibroblasts following IL-22 stimulation in vitro. Furthermore, knockdown of PLCε with its siRNA decreased expression of IL-1α, CCL20, and S100 proteins, and MBD3 in HEK cultures. Collectively, these results suggested that PLCε mediated cytokine cascade induced by acute barrier disruption. IL-22 is likely the upstream of PLCε-mediated cytokine cascade following acute barrier disruption.

【 授权许可】

Unknown