The intracellular signal cascades involved in chemokine-stimulated migration of in vitro activated human peripheral blood CD4+ T-lymphocytes were investigated. IP-10-mediated chemotactic response of lymphocytes was decreased in the presence of selective inhibitors of Src-kinases (by 40-45%), PI3-kinases (35-40%), and MAP-kinases ERK1/2 (35-40%) and p38 (20%). Combined addition of specific inhibitors of Src-kinases and PI3-kinases and inhibitors of Src-kinases and ERK1/2 MAP-kinases did not result in the further increase of the inhibitory effect, while the combined addition of specific inhibitors of PI3-kinases and ERK1/2 MAP-kinases decreased migration of CD4+ T-lymphocytes more effectively (by 55-60%) than any individual inhibitor. Immunoblotting analysis of activation of MAP-kinases ERK1/2 and p38 revealed increased level of phosphorylation of ERK1/2 and p38 MAP-kinases in the presence IP-10. Selective inhibitors of Src-kinases and PI3-kinases significantly inhibited phosphorylation of p38 but did not influence phosphorylation of ERK1/2 MAP-kinases. Our results suggest that Src-kinases, PI3-kinases, and ERK1/2 MAP-kinases are involved in intracellular signal cascade activated during IP-10-stimulated migration of T-lymphocytes, whereas p38 MAP-kinases do not participate in the migration process, although its activation induced by IP-10 depends on Src-kinases and PI3-kinases.
Ingramon treatment was accompanied by less pronounced elevation of hsCRP and fibrinogen levels and decreased MCP-1 concentration in plasma in patients after coronary stenting. Ingramon had no effect on MCP-1 interaction with cell receptors or MCP-1 dimerization, but inhibited MCP-1 binding to heparin. The anti-inflammatory activity of the peptide may be mediated by an impaired chemokine interaction with glycosaminoglycans.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.