Tumour necrosis factor‐like weak inducer of apoptosis (TWEAK), an important mediator of endothelial inflammation, is associated with the pathogenesis of Henoch–Schonlein purpura

• Published in: Clinical and experimental immunology Vol. 166; no. 1; pp. 64 - 71
• Main Authors: Chen, T., Guo, Z‐P., Li, M‐M., Li, J‐Y., Jiao, X‐Y., Zhang, Y‐H., Liu, H‐J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2011; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adolescent; Adult; Analytical, structural and metabolic biochemistry; Apoptosis; Apoptosis - drug effects; Apoptosis - immunology; Atopic dermatitis; Biological and medical sciences; Blotting, Western; Case-Control Studies; Cell migration; Cells, Cultured; Chemokine CCL5 - biosynthesis; Chemokine CCL5 - immunology; Chemokines; Child; Child, Preschool; Cytokine TWEAK; Cytokines; Data processing; Dermatitis, Atopic - immunology; Dermatitis, Atopic - metabolism; Dermatitis, Atopic - pathology; Dermatology; Drug therapy; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - immunology; Endothelial Cells - pathology; Enzyme-linked immunosorbent assay; Female; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Heat shock proteins; Henoch–Schonlein purpura; Humans; I-kappa B Proteins - immunology; I-kappa B Proteins - metabolism; Immune system; Infectious diseases; Inflammation; Inflammation - immunology; Inflammation - metabolism; Inflammation - pathology; Interleukin-8 - biosynthesis; Interleukin-8 - immunology; Leukocyte migration; Leukocytes; Male; Medical sciences; Microvasculature; Monocytes; mRNA; NF- Kappa B protein; NF-kappa B - antagonists & inhibitors; NF-kappa B - immunology; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; Phosphorylation; Polymerase Chain Reaction; Psoriasis - immunology; Psoriasis - metabolism; Psoriasis - pathology; psoriasis vulgaris; Purpura; Purpura, Schoenlein-Henoch - immunology; Purpura, Schoenlein-Henoch - metabolism; Purpura, Schoenlein-Henoch - pathology; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Serum levels; Signal Transduction - drug effects; Signal Transduction - immunology; Skin; Skin - drug effects; Skin - immunology; Skin - pathology; Translational Studies; Tumor necrosis factor; Tumor Necrosis Factors - biosynthesis; Tumor Necrosis Factors - immunology; Tumor Necrosis Factors - pharmacology; tumour necrosis factor‐like weak inducer of apoptosis; TWEAK protein; Vascular disorders of the skin; Vasculitis; Western blotting; tumour necrosis factor-like weak inducer of apoptosis; Skin disease; Endothelial cell; endothelial cells; Pathogenesis; Cytokine; Diseases of the osteoarticular system; Cardiovascular disease; Henoch—Schonlein purpura; Biochemistry; Inflammation; chemokines; Vascular disease; Chemokine; Association; Tumor necrosis factor; Cell death; Henoch-Schönlein purpura; Capillary vessel disease; Apoptosis
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2011.04442.x

Summary 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.