TY - JOUR
T1 - Molecular regulation of interleukin-13 and monocyte chemoattractant protein-1 expression in human mast cells by interleukin-1β
AU - Lee, Steven A.
AU - Fitzgerald, S. Matthew
AU - Huang, Shau K.
AU - Li, Chuanfu
AU - Chi, David S.
AU - Milhorn, Denise M.
AU - Krishnaswamy, Guha
PY - 2004/9
Y1 - 2004/9
N2 - Mast cells play pivotal roles in immunoglobulin (Ig) E-mediated airway inflammation, expressing interleukin (IL)-13 and monocyte chemoattractant protein-1 (MCP-1), which in turn regulate IgE synthesis and/or inflammatory cell recruitment. The molecular effects of IL-1β on cytokine expression by human mast cells (HMC) have not been studied well. In this report, we provide evidence that human umbilical cord blood-derived mast cells (CBDMC) and HMC-1 cells express the type 1 receptor for IL-1. We also demonstrate that IL-1β and tumor necrosis factor-α are able to induce, individually or additively, dose-dependent expression of IL-13 and MCP-1 in these cells. The induction of IL-13 and MCP-1 gene expression by IL-1β was accompanied by the activation of IL-1 receptor-associated kinase and translocation of the transcription factor, nuclear factor (NF) κB into the nucleus. Accordingly, Bay-11 7082, an inhibitor of NF-κB activation, inhibited IL-1β-induced IL-13 and MCP-1 expression. IL-1β also induced IL-13 promoter activity while enhancing the stability of IL-13 messenger RNA transcripts. Dexamethasone, a glucocorticoid, inhibited IL-1β-induced nuclear translocation of NF-κB and also the secretion of IL-13 from mast cells. Our data suggest that IL-1β can serve as a pivotal costimulus of inflammatory cytokine synthesis in human mast cells, and this may be partly mediated by IL-1 receptor-binding and subsequent signaling via nuclear translocation of NF-κB. Because IL-1β is a ubiquitously expressed cytokine, these findings have important implications for non-IgE-mediated signaling in airway mast cells as well as for innate immunity and airway inflammatory responses, such as observed in extrinsic and intrinsic asthma.
AB - Mast cells play pivotal roles in immunoglobulin (Ig) E-mediated airway inflammation, expressing interleukin (IL)-13 and monocyte chemoattractant protein-1 (MCP-1), which in turn regulate IgE synthesis and/or inflammatory cell recruitment. The molecular effects of IL-1β on cytokine expression by human mast cells (HMC) have not been studied well. In this report, we provide evidence that human umbilical cord blood-derived mast cells (CBDMC) and HMC-1 cells express the type 1 receptor for IL-1. We also demonstrate that IL-1β and tumor necrosis factor-α are able to induce, individually or additively, dose-dependent expression of IL-13 and MCP-1 in these cells. The induction of IL-13 and MCP-1 gene expression by IL-1β was accompanied by the activation of IL-1 receptor-associated kinase and translocation of the transcription factor, nuclear factor (NF) κB into the nucleus. Accordingly, Bay-11 7082, an inhibitor of NF-κB activation, inhibited IL-1β-induced IL-13 and MCP-1 expression. IL-1β also induced IL-13 promoter activity while enhancing the stability of IL-13 messenger RNA transcripts. Dexamethasone, a glucocorticoid, inhibited IL-1β-induced nuclear translocation of NF-κB and also the secretion of IL-13 from mast cells. Our data suggest that IL-1β can serve as a pivotal costimulus of inflammatory cytokine synthesis in human mast cells, and this may be partly mediated by IL-1 receptor-binding and subsequent signaling via nuclear translocation of NF-κB. Because IL-1β is a ubiquitously expressed cytokine, these findings have important implications for non-IgE-mediated signaling in airway mast cells as well as for innate immunity and airway inflammatory responses, such as observed in extrinsic and intrinsic asthma.
UR - http://www.scopus.com/inward/record.url?scp=4444358455&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4444358455&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2004-0089OC
DO - 10.1165/rcmb.2004-0089OC
M3 - Article
C2 - 15191916
AN - SCOPUS:4444358455
SN - 1044-1549
VL - 31
SP - 283
EP - 291
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
IS - 3
ER -