title: Tumour necrosis factor-like weak inducer of apoptosis (TWEAK), an important mediator of endothelial inflammation, is associated with the pathogenesis of Henoch-Schonlein purpura.
abstract: Tumour necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumour necrosis factor (TNF) family, has been implicated as a proinflammatory cytokine in many types of autoimmune and infectious diseases. However, information about TWEAK in dermatological diseases is limited. Herein, we investigated the role of TWEAK in patients with Henoch-Schonlein purpura (HSP) and the ability of TWEAK on chemokine production in the human dermal microvascular endothelial cell line (HMEC-1). Serum TWEAK levels in patients with HSP, together with patients with psoriasis vulgaris (PV) and atopic dermatitis (AD), were detected by enzyme-linked immunosorbent assay (ELISA). HMEC-1 cells were treated with TWEAK at concentrations ranging from 1 ng/ml to 100 ng/ml. Serum levels of TWEAK were elevated in patients with HSP in the acute stage but not in patients with PV or AD. Moreover, TWEAK levels were correlated with the severity of HSP. TWEAK markedly induced CCL5 and CXCL8 production at both mRNA and protein levels in HMEC-1 cells. In addition, TWEAK-stimulated HMEC-1 supernatant enhanced HL-60 or human acute monocytic leukaemia cell line (THP-1) cell migration. Finally, Western blot data revealed that TWEAK can induce rapid phosphorylation of inhibitor of κB-α (IκBα) in HMEC-1 cells. In conclusion, we show that serum levels of TWEAK were elevated in patients with acute stage HSP. TWEAK may act as a regulator of nuclear factor-κB (NF-κB) activation and chemokine production in human dermal microvascular endothelial cells, thus promoting leucocyte migration in cutaneous vasculitis.
authors.affiliation: Department of Dermatovenereology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.forename: Z-P
authors.initials: ZP
authors.lastname: Guo
authors.forename: M-M
authors.initials: MM
authors.lastname: Li
authors.forename: J-Y
authors.initials: JY
authors.lastname: Li
authors.forename: X-Y
authors.initials: XY
authors.lastname: Jiao
authors.forename: Y-H
authors.initials: YH
authors.lastname: Zhang
authors.forename: H-J
authors.initials: HJ
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D000074049:Cytokine TWEAK; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000276:immunology / Q000378:metabolism; D011695:IgA Vasculitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D048069:Tumor Necrosis Factors / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology
chemical_list: C483024:CCL5 protein, human; C508606:CXCL8 protein, human; D018946:Chemokine CCL5; D000074049:Cytokine TWEAK; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors; D000072000:NF-KappaB Inhibitor alpha