Interleukin-3,-5, and granulocyte macrophage colony stimulating factor induce adhesion and chemotaxis of human eosinophils via p38 mitogenin activated protein kinase and nuclear factor kappa B
Publication in refereed journal


摘要Hematopoietic cytokines such as interleukin (IL)-3, IL-5, and granulocyte macrophage colony-stimulating factor (GM-CSF) play a fundamental role in eosinophil functions in allergic asthma. The intracellular signal transduction mechanisms of these cytokines regulating the activation of eosinophils have been potential therapeutic targets. We investigated the roles of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-kappa B) in IL-3, IL-5, and GM-CSF-induced adhesion, morphological changes, and subsequence transmigration of human eosinophils. IL-3, IL-5, and GMCSF could augment the phosphorylation of p38 MAPK and nucleus translocation of NF-kappa B in eosinophils. cDNA expression arrays demonstrated that the gene expression levels of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1), alpha 6, beta 2 integrin (CD18), and CD44 were upregulated by these cytokines. Results from functional assays showed that adhesion of eosinophils onto airway epithelial cells was enhanced after IL-3 and IL-5 but not GM-CSF stimulation. These cytokines could markedly induce shape change and augment the transmigration of eosinophils. Moreover, administration of either p38 MAPK inhibitor, SB 203580, or proteasome inhibitor, N-cbz-Leu-Leu-leucinal (MG-132), could inhibit the cytokine-induced adhesion, shape change, and transmigration of eosinophils. Together, our findings suggest that IL-3, IL-5, and GM-CSF regulated the adhesion and chemotaxis of human eosinophils through shared signaling pathways involving both p38 MAPK and NF-kappa B. Our results therefore shed light on the further development of more effective agents for allergic and inflammatory diseases.
著者Ip WK, Wong CK, Wang CB, Tian YP, Lam CWK
期刊名稱Immunopharmacology and Immunotoxicology
頁次371 - 393
關鍵詞adhesion; chemotaxis; eosinophil; GM-CSF; IL-3 and IL-5; NF-kappa B; p38 MAPK
Web of Science 學科類別Immunology; IMMUNOLOGY; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY; Toxicology; TOXICOLOGY

上次更新時間 2020-27-10 於 02:10