| First Author | Bocian C | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 18 | Pages | 12699-711 |
| PubMed ID | 23460644 | Mgi Jnum | J:198278 |
| Mgi Id | MGI:5496295 | Doi | 10.1074/jbc.M112.419366 |
| Citation | Bocian C, et al. (2013) Decorin potentiates interferon-gamma activity in a model of allergic inflammation. J Biol Chem 288(18):12699-711 |
| abstractText | 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-gamma (Ifn-gamma) 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-alpha stimulation. However, Dcn(-/-) and wild-type lymphocytes produced IFN-gamma after activation with CD3epsilon. Upon incubation with decorin, endothelial cells and fibroblasts responded differently to IFN-gamma and TNF-alpha; CCL2 in bEnd.3 cells was more prominently up-regulated by TNF-alpha compared with IFN-gamma. Notably, both factors were more potent in the presence of decorin. Compared with TNF-alpha, IFN-gamma treatment induced significantly more CXCL-10, and both factors increased synthesis of CXCL-10 in the presence of decorin. The response to IFN-gamma 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-gamma in vitro and potentiated IFN-gamma-induced activation of STAT-1. Furthermore, only dermatan sulfate influenced IFN-gamma 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-gamma and TNF-alpha, thereby influencing the recruitment of CD8(+) lymphocytes into the inflamed tissue. |
