TY - JOUR
T1 - Activation of eosinophils by IL-12 family cytokine IL-27
T2 - Implications of the pleiotropic roles of IL-27 in allergic responses
AU - Hu, Shuiqing
AU - Wong, Chun Kwok
AU - Lam, Christopher Wai Kei
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Chemokines
KW - Cytokines
KW - Eosinophils
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=78649522921&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649522921&partnerID=8YFLogxK
U2 - 10.1016/j.imbio.2010.03.004
DO - 10.1016/j.imbio.2010.03.004
M3 - Article
C2 - 20435369
AN - SCOPUS:78649522921
SN - 0171-2985
VL - 216
SP - 54
EP - 65
JO - Immunobiology
JF - Immunobiology
IS - 1-2
ER -