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1	Molecular Regulation of Interleukin-13 and Monocyte Chemoattractant Protein-1 Expression in Human Mast Cells by Interleukin-1beta Lee, Steven A., Fitzgerald, S M., Huang, Shau K., Li, Chuanfu, Chi, David S., Milhorn, Denise M., Krishnaswamy, Guha 01 September 2004 (has links) 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-1beta 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-1beta and tumor necrosis factor-alpha 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-1beta was accompanied by the activation of IL-1 receptor-associated kinase and translocation of the transcription factor, nuclear factor (NF) kappaB into the nucleus. Accordingly, Bay-11 7082, an inhibitor of NF-kappaB activation, inhibited IL-1beta-induced IL-13 and MCP-1 expression. IL-1beta also induced IL-13 promoter activity while enhancing the stability of IL-13 messenger RNA transcripts. Dexamethasone, a glucocorticoid, inhibited IL-1beta-induced nuclear translocation of NF-kappaB and also the secretion of IL-13 from mast cells. Our data suggest that IL-1beta 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-kappaB. Because IL-1beta 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. active transport cell nucleus (drug effects genetics) cell line chemokine CCL2 (genetics immunology metabolism) dexamethasone (pharmacology) dose-response relationship drug drug synergism enzyme inhibitors (pharmacology) gene expression regulation (drug effects genetics) humans interleukin-1 (immunology metabolism pharmacology) interleukin-13 (genetics immunology metabolism) mast cells (drug effects immunology metabolism) NF-kappa B (metabolism) protein kinases (metabolism) RNA messenger (drug effects metabolism) receptors interleukin-1 (immunology metabolism) receptors interleukin-1 type I tumor necrosis factor-alpha (immunology metabolism pharmacology) Internal Medicine

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Molecular Regulation of Interleukin-13 and Monocyte Chemoattractant Protein-1 Expression in Human Mast Cells by Interleukin-1beta