Activation of eosinophils by IL-12 family cytokine IL-27: Implications of the pleiotropic roles of IL-27 in allergic responses.
Interleukin (IL)-27 is a novel IL-12 family cytokine and its immunomodulatory effects on T-lymphocytes, B-lymphocytes and mast cells were extensively studied. IL-27 could suppress Th2-mediated allergic diseases in mouse models. However, the role of IL-27 on eosinophils, the principal effector cells in allergic diseases, remains unexplored. Our present study revealed that eosinophils constitutively express functional IL-27 receptor heterodimer, gp130 and WSX-1. IL-27 could prolong eosinophil survival by reducing apoptosis, modulate the expression of adhesion molecules to facilitate eosinophil adhesion and accumulation, and induce the release of proinflammatory cytokines IL-6, tumor necrosis factor-α, IL-1β and chemokines CCL2, CXCL8 and CXCL1. The stimulation effects of IL-27 on eosinophils could not be abrogated by Th2 cytokine IL-25, hematopoietic cytokine granulocyte macrophage colony-stimulating factor, and toll-like receptor 4 ligand lipopolysaccharide (LPS). These findings are different from the effects of IL-27 and LPS on monocytes. Intracellular signaling mechanistic studies showed that IL-27-mediated eosinophil activation was differentially regulated by the activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase, as well as nuclear factor-κB. Based on the above results, IL-27 could play crucial roles in allergic diseases by the activation of eosinophils via differential intracellular signaling cascades. According to the present findings of its activating effects on human eosinophils, IL-27 may play pleiotropic roles in human allergic responses.
Hu
Shuiqing
S
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Wong
Chun Kwok
CK
Lam
Christopher Wai Kei
CW
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
D015815:Cell Adhesion Molecules; D016207:Cytokines; C112441:IL27RA protein, human; D018836:Inflammation Mediators; D007378:Interleukins; C464565:MYDGF protein, human; D016328:NF-kappa B; D018123:Receptors, Interleukin; D018664:Interleukin-12; D048049:Extracellular Signal-Regulated MAP Kinases