PMID- 15191916
OWN - NLM
STAT- MEDLINE
DCOM- 20041005
LR  - 20131121
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 31
IP  - 3
DP  - 2004 Sep
TI  - Molecular regulation of interleukin-13 and monocyte chemoattractant protein-1 
      expression in human mast cells by interleukin-1beta.
PG  - 283-91
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-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.
FAU - Lee, Steven A
AU  - Lee SA
AD  - Department of Internal Medicine, East Tennessee State University, Johnson City, 
      Tennessee 37614-1709, USA.
FAU - Fitzgerald, S Matthew
AU  - Fitzgerald SM
FAU - Huang, Shau K
AU  - Huang SK
FAU - Li, Chuanfu
AU  - Li C
FAU - Chi, David S
AU  - Chi DS
FAU - Milhorn, Denise M
AU  - Milhorn DM
FAU - Krishnaswamy, Guha
AU  - Krishnaswamy G
LA  - eng
GR  - AI-43310/AI/NIAID NIH HHS/United States
GR  - HL-63070/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040610
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-13)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (Receptors, Interleukin-1 Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects/genetics
MH  - Cell Line
MH  - Chemokine CCL2/genetics/immunology/*metabolism
MH  - Dexamethasone/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Humans
MH  - Interleukin-1/immunology/*metabolism/pharmacology
MH  - Interleukin-1 Receptor-Associated Kinases
MH  - Interleukin-13/genetics/immunology/*metabolism
MH  - Mast Cells/drug effects/immunology/*metabolism
MH  - NF-kappa B/metabolism
MH  - Protein Kinases/metabolism
MH  - RNA, Messenger/drug effects/metabolism
MH  - Receptors, Interleukin-1/immunology/metabolism
MH  - Receptors, Interleukin-1 Type I
MH  - Tumor Necrosis Factor-alpha/immunology/*metabolism/pharmacology
EDAT- 2004/06/12 05:00
MHDA- 2004/10/06 09:00
CRDT- 2004/06/12 05:00
PHST- 2004/06/12 05:00 [pubmed]
PHST- 2004/10/06 09:00 [medline]
PHST- 2004/06/12 05:00 [entrez]
AID - 2004-0089OC [pii]
AID - 10.1165/rcmb.2004-0089OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2004 Sep;31(3):283-91. doi: 10.1165/rcmb.2004-0089OC. 
      Epub 2004 Jun 10.