Intracellular signal cascade in CD4+ T-lymphocyte migration stimulated by interferon-gamma-inducible protein-10

• Published in: Biochemistry (Moscow) 2005-06, Vol.70 (6), p.652-656
• Main Authors: Kukhtina, N B, Arefieva, T I, Krasnikova, T L
• Format: Article
• Language: English
• Subjects: Calcium-Calmodulin-Dependent Protein Kinases; CD4-Positive T-Lymphocytes - cytology; Cell Movement - drug effects; Cell Movement - physiology; Cellular Apoptosis Susceptibility Protein - analysis; Chemokine CXCL10; Chemokines, CXC - pharmacology; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Humans; Lymphocyte Activation; MAP Kinase Signaling System - immunology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphorylation; Signal Transduction - immunology; src-Family Kinases - antagonists & inhibitors
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1007/s10541-005-0165-5

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.