Leptin-mediated cytokine release and migration of eosinophils: implications for immunopathophysiology of allergic inflammation.
Leptin is a pleiotropic adipocyte-derived cytokine used in hypothalamic regulation of body weight and modulation of immune response by stimulating T cells, macrophages and neutrophils. Leptin has been shown to be an eosinophil survival factor. We examined the immunopathological mechanisms for the activation of human eosinophils from healthy volunteers by leptin in allergic inflammation. Adhesion molecules, cytokines and cell migration were assessed by flow cytometry, ELISA and Boyden chamber assay, respectively. Intracellular signaling molecules were investigated by membrane array and Western blot. Leptin could up-regulate cell surface expression of adhesion molecule ICAM-1 and CD18 but suppress ICAM-3 and L-selectin on eosinophils. Leptin could also stimulate the chemokinesis of eosinophils, and induce the release of inflammatory cytokines IL-1beta and IL-6, and chemokines IL-8, growth-related oncogene-alpha and MCP-1. We found that leptin-mediated induction of adhesion molecules, release of cytokines and chemokines, and chemokinesis were differentially regulated by the activation of ERK, p38 MAPK and NF-kappaB. In view of the above results and elevated production of leptin in patients with allergic diseases such as atopic asthma and atopic dermatitis, leptin could play crucial immunopathophysiological roles in allergic inflammation by activation of eosinophils via differential intracellular signaling cascades.
Wong
Chun Kwok
CK
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Cheung
Phyllis F-Y
PF
Lam
Christopher W K
CW
D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D004789:Enzyme Activation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D020738:Leptin / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D015815:Cell Adhesion Molecules; D016207:Cytokines; D020738:Leptin; D016328:NF-kappa B; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases