Interleukin-3, -5, and granulocyte macrophage colony-stimulating factor-induced adhesion molecule expression on eosinophils by p38 mitogen-activated protein kinase and nuclear factor-[kappa] B.
We investigated the intracellular signaling mechanisms for cytokine interleukin (IL)-3, IL-5, or granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced expression of adhesion molecules including very late antigen 4 (CD49 d), macrophage antigen-1 (CD11b), leukocyte function-associated antigen-1 (CD11a/CD18), intercellular adhesion molecule (ICAM)-1, and ICAM-3 on eosinophils. The expression of adhesion molecules and nuclear factor (NF)-kappaB pathway was measured by flow cytometry and cDNA expression array, respectively. The phosphorylation of inhibitor kappaB-alpha and p38 mitogen-activated protein kinase (MAPK) was detected by Western blot, whereas NF-kappaB activity was measured by electrophoretic mobility shift assay. IL-3, IL-5, and GM-CSF could enhance p38 MAPK and NF-kappaB activity and induce ICAM-1, CD11b, and CD18 expressions on eosinophils. They could suppress ICAM-3 expression, but had no effect on CD49 d expression. Either SB 203580 or MG-132 was able to offset the cytokine-induced expression of ICAM-1. Only SB 203580 could reverse the effect on CD11b, CD18, and ICAM-3 expressions. Therefore, the expression of ICAM-1 might involve both p38 MAPK and NF-kappaB activities, whereas the regulation of CD11b, CD18, and ICAM-3 expressions might be mediated through p38 MAPK but not NF-kappaB. These cytokines therefore play a crucial role, via the p38 MAPK and NF-kappaB pathways, in the expression of important adhesion molecules on eosinophils in allergic inflammation.
Wong
Chun K
CK
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Ip
Wai K
WK
Lam
Christopher W K
CW
D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D039441:Integrin alpha4 / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism / Q000494:pharmacology*; D015848:Interleukin-5 / Q000378:metabolism / Q000494:pharmacology*; D007976:Leupeptins / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases
D039481:CD11b Antigen; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007377:Interleukin-3; D015848:Interleukin-5; D007976:Leupeptins; D016328:NF-kappa B; D011725:Pyridines; D039441:Integrin alpha4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde