title: Decorin potentiates interferon-γ activity in a model of allergic inflammation.
abstract: The proteoglycan decorin modulates leukocyte recruitment during delayed-type hypersensitivity responses. Decorin-deficient (Dcn(-/-)) mice show reduced edema formation during the first 24 h with a concurrent attenuated recruitment of CD8(+) leukocytes in the inflamed Dcn(-/-) ears. The aim of this study was to elucidate the molecular pathways affected by the loss of decorin. In vivo, reduced numbers of CD8(+) cells in Dcn(-/-) ears correlated with a reduced interferon-γ (Ifn-γ) and CXCL-10 expression. In vitro, Dcn(-/-) lymphocytes displayed an increased adhesion to brain microvascular (bEnd.3) endothelial cells. Decorin treatment of bEnd.3 increased Icam1 and down-regulated Vcam1 expression after TNF-α stimulation. However, Dcn(-/-) and wild-type lymphocytes produced IFN-γ after activation with CD3ε. Upon incubation with decorin, endothelial cells and fibroblasts responded differently to IFN-γ and TNF-α; CCL2 in bEnd.3 cells was more prominently up-regulated by TNF-α compared with IFN-γ. Notably, both factors were more potent in the presence of decorin. Compared with TNF-α, IFN-γ treatment induced significantly more CXCL-10, and both factors increased synthesis of CXCL-10 in the presence of decorin. The response to IFN-γ was similar in Dcn(-/-) and wild-type fibroblasts, an additional source of CXCL-10. However, addition of decorin yielded significantly more CXCL-10. Notably, decorin increased the stability of IFN-γ in vitro and potentiated IFN-γ-induced activation of STAT-1. Furthermore, only dermatan sulfate influenced IFN-γ signaling by significantly increasing CXCL-10 expression in contrast to decorin protein core alone. Our data demonstrate that decorin modulates delayed-type hypersensitivity responses by augmenting the induction of downstream effector cytokines of IFN-γ and TNF-α, thereby influencing the recruitment of CD8(+) lymphocytes into the inflamed tissue.
authors: Institute of Physiological Chemistry and Pathobiochemistry, Waldeyerstrasse 15, 48149 Münster, Germany.
authors: Carla
authors: C
authors: Bocian
authors: Ann-Kathrin
authors: AK
authors: Urbanowitz
authors: Rick T
authors: RT
authors: Owens
authors: Renato V
authors: RV
authors: Iozzo
authors: Martin
authors: M
authors: Götte
authors: Daniela G
authors: DG
authors: Seidler
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D058575:Decorin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D017252:CD3 Complex; C491768:Ccl2 protein, mouse; C485468:Cd3e protein, mouse; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; C546879:Dcn protein, mouse; D058575:Decorin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Chondroitin Sulfate; Cytokine; Dermatan Sulfate; Inflammation; Proteoglycan