IL-25, a member of the IL-17 cytokine family, is known to enhance Th2-like responses associated with increased serum levels of IgE, IgG1, IgA, blood eosino - philia, and eosinophilic infiltrates in various tissues. However, IL-25 also abrogates inflammatory responses driven by Th17 cells. However, the cell types that respond to IL-25 and the mechanisms by which IL-25 differentially regulates immune reactions are not well explored. To identify potential targets of IL-25, we initially examined IL-25 receptor (IL-25R) in human peripheral blood cells. IL-25R was predominantly expressed by CD14+ cells. We next assessed the functional role of IL-25 in modulating the response of CD14+ cells to various inflammatory signals. CD14+ cells responded to IL-25 by down - regulating the synthesis of inflammatory cytokines induced by toll-like receptor (TLR) ligands and inflammatory cyto - kines. Inhibition of cytokine response by IL-25 occurred via a p38 Map kinase - driven Socs-3-dependent mechanism. In vivo, IL-25 inhibited monocyte-derived cy - tokines and protected against LPS - induced lethal endotoxemia in mice. These data indicate that IL-25 is a negative regulator of monocyte proinflammatory cytokine responses, which may have therapeutic implications. © 2009 by The American Society of Hematology.
Inhibition of monocyte-derived inflammatory cytokines by IL-25 occurs via a p38 Map kinase-dependent induction of SOCS-3
FANTINI M;
2009-01-01
Abstract
IL-25, a member of the IL-17 cytokine family, is known to enhance Th2-like responses associated with increased serum levels of IgE, IgG1, IgA, blood eosino - philia, and eosinophilic infiltrates in various tissues. However, IL-25 also abrogates inflammatory responses driven by Th17 cells. However, the cell types that respond to IL-25 and the mechanisms by which IL-25 differentially regulates immune reactions are not well explored. To identify potential targets of IL-25, we initially examined IL-25 receptor (IL-25R) in human peripheral blood cells. IL-25R was predominantly expressed by CD14+ cells. We next assessed the functional role of IL-25 in modulating the response of CD14+ cells to various inflammatory signals. CD14+ cells responded to IL-25 by down - regulating the synthesis of inflammatory cytokines induced by toll-like receptor (TLR) ligands and inflammatory cyto - kines. Inhibition of cytokine response by IL-25 occurred via a p38 Map kinase - driven Socs-3-dependent mechanism. In vivo, IL-25 inhibited monocyte-derived cy - tokines and protected against LPS - induced lethal endotoxemia in mice. These data indicate that IL-25 is a negative regulator of monocyte proinflammatory cytokine responses, which may have therapeutic implications. © 2009 by The American Society of Hematology.
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