title: Diminished production of TWEAK by the peripheral blood mononuclear cells is associated with vascular involvement in patients with systemic sclerosis.
abstract: Widespread vasculopathy and profound fibrosis are key features of the pathogenesis of systemic sclerosis (SSc). We hypothesized that the TNF-like weak inducer of apoptosis (TWEAK), a recently recognized multifunctional cytokine which regulates angiogenesis and tissue remodeling, may play a role in the development of SSc. The production of TWEAK by the peripheral blood mononuclear cells (PBMC) was investigated, by means of ELISA, in 24 SSc patients and 14 healthy subjects. Moreover, production of TWEAK was correlated with clinical features of SSc. PBMC were isolated using density gradient centrifugation on Histopaque and were cultured in FCS supplemented RPMI medium at 37 degrees C under 5% CO2. Production of TWEAK by PBMC was significantly diminished in patients with more severe microvascular damage, as indicated by the presence of "active" capillaroscopic pattern, compared with SSc patients with less pronounced microangiopathy ("slow" pattern), and healthy subjects. Moreover production of TWEAK correlated inversely with duration of Raynaud's phenomenon. PBMC from patients with scleroderma-related interstitial lung disease tended to produce lower amounts of TWEAK compared with SSc patients without lung involvement but the difference was not significant. The results of our study suggest that diminished production of TWEAK might play a role in the pathogenesis of vascular injury in SSc patients. Whether TWEAK may represent a new therapeutic target in SSc requires further studies.
authors.affiliation: Department of Orthopedics, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bielecki
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kowal
authors.forename: Anna
authors.initials: A
authors.lastname: Lapinska
authors.forename: Justyna
authors.initials: J
authors.lastname: Chwiecko
authors.forename: Jan
authors.initials: J
authors.lastname: Skowronski
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Sierakowski
authors.forename: Lech
authors.initials: L
authors.lastname: Chyczewski
authors.forename: Otylia
authors.initials: O
authors.lastname: Kowal-Bielecka
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D000074049:Cytokine TWEAK; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D055806:Microvessels / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology; D048069:Tumor Necrosis Factors / Q000096:biosynthesis*
chemical_list: D000074049:Cytokine TWEAK; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors