Journal of Leukocyte Biology | |
Heparin-disaccharide affects T cells: inhibition of NF-κB activation, cell migration, and modulation of intracellular signaling | |
Iris Hecht2  Liora Cahalon2  Rami Hershkoviz1  Irun R. Cohen2  Tzvi Lapidot2  Shoham Shivtiel2  Ofer Lider2  | |
[1] The Sakler Faculty of Medicine, Tel-Aviv University, Israel The Sakler Faculty of Medicine, Tel-Aviv University, Israel The Sakler Faculty of Medicine, Tel-Aviv University, Israel;Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; and Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; and Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; and | |
关键词: chemokines; CXCL12; extracellular matrix; TNF-α; IFN-γ; | |
DOI : 10.1189/jlb.1203659 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
We previously reported that disaccharides (DS), generated by enzymatic degradation of heparin or heparan sulfate, inhibit T cell-mediated immune reactions in rodents and regulate cytokine [tumor necrosis factor α (TNF-α), interleukin (IL)-8, and IL-1β] secretion by T cells, macrophages, or intestinal epithelial cells. Here, we investigated the effects of a trisulfated heparin DS (3S-DS) on two aspects of T cell function: secretion of proinflammatory cytokines and migration to an inflamed site. 3S-DS down-regulated nuclear factor-κB activity and reduced the secretion of TNF-α and interferon-γ (IFN-γ) by anti-CD3-activated T cells. In addition, 3S-DS inhibited CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor-1α)-dependent migration in vitro and in vivo and decreased CXCL12-induced T cell adhesion to the extracellular matrix glycoprotein, fibronectin (FN). This inhibition was accompanied by attenuation of CXCL12-induced Pyk2 phosphorylation but did not involve internalization of the CXCL12 receptor, CXCR4, or phosphorylation of extracellular-regulated kinase. Despite inhibiting CXCL12-induced adhesion, 3S-DS, on its own, induced T cell adhesion to FN, which was accompanied by phosphorylation of Pyk2. A monosulfated DS showed no effect. Taken together, these data provide evidence that 3S-DS can regulate inflammation by inducing and modulating T cell-signaling events, desensitizing CXCR4, and modulating T cell receptor-induced responses.
【 授权许可】
Unknown
【 预 览 】
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