title: IL-17A induces endothelial inflammation in systemic sclerosis via the ERK signaling pathway.
abstract: Recent reports have demonstrated that endothelial cells are involved in vascular inflammatory injury in systemic sclerosis (SSc) and interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of SSC. However, little is known about the effects of IL-17A on endothelial cell inflammation in SSC. The aim of our study was to investigate the role of IL-17A in endothelial inflammation. Here, we showed that IL-17A mRNA and protein levels were augmented in the peripheral blood and more IL-17⁺ lymphocytes infiltrated in the perivascular areas in the involved skin of SSC patients. SSC patient serum induced chemokine and adhesion molecule expression in HUVECs, which was blocked by IL-17A neutralization. IL-17A alone induced chemokine and adhesion molecule expression and promoted T cell-HUVEC adhesion. Extracellular signal-regulated kinase (ERK) inhibition and IL-17A neutralization prominently inhibited chemokine and adhesion molecule expression and blocked T cell-HUVEC adhesion. IL-17A derived from SSC patient serum mediated endothelial cells inflammation by up-regulating chemokines and adhesion molecules, which was blocked by ERK inhibition. These data imply that ERK signal pathway might play a key role in the progression of endothelial injury induced by IL-17A in SSC.
authors.affiliation: Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Xing
authors.affiliation: Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Lubing
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Di
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D018925:Chemokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012595:Scleroderma, Systemic / Q000150:complications / Q000503:physiopathology*
chemical_list: D018925:Chemokines; D017931:DNA Primers; C508717:IL17A protein, human; D020381:Interleukin-17