PMID- 16792687
OWN - NLM
STAT- MEDLINE
DCOM- 20060807
LR  - 20181113
IS  - 0009-9104 (Print)
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Linking)
VI  - 145
IP  - 1
DP  - 2006 Jul
TI  - Interleukin (IL)-4 and IL-13 up-regulate monocyte chemoattractant protein-1 
      expression in human bronchial epithelial cells: involvement of p38 
      mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2 and 
      Janus kinase-2 but not c-Jun NH2-terminal kinase 1/2 signalling pathways.
PG  - 162-72
AB  - The Th2 cytokines interleukin (IL)-4 and IL-13 and chemokine monocyte 
      chemoattractant protein-1 (MCP-1) are significantly involved in bronchial 
      hyperreactivity (BHR) and remodelling in allergic asthma. Although IL-4 and IL-13 
      can regulate a number of chemokines from bronchial epithelium, their regulatory 
      effect on the expression of MCP-1 is as yet unproved. We aim to investigate the 
      intracellular signalling mechanisms of IL-4 and IL-13 regulating the expression 
      and secretion of MCP-1 from human bronchial epithelial cells. BEAS-2B cells, 
      derived from a human bronchial epithelial cell line, were activated with or 
      without IL-4 and/or IL-13 for different time intervals. MCP-1 gene expression and 
      protein secretion were measured by reverse transcription-polymerase chain 
      reaction and enzyme-linked immunosorbent assay, respectively. Activation of 
      signalling molecules p38 mitogen-activated protein kinase (MAPK), extracellular 
      signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and Janus kinase-2 
      (JAK-2) was accessed by Western blotting. IL-4 and IL-13 were found to 
      up-regulate gene expression and significantly increase the release of MCP-1 from 
      BEAS-2B cells. Both cytokines could activate p38 MAPK, ERK and JAK-2, but not JNK 
      activity. Inhibition of p38 MAPK, ERK and JAK-2 activities by pretreating the 
      cells with their corresponding inhibitors SB203580, PD98059 and AG490, 
      respectively, significantly suppressed IL-4- and IL-13-induced MCP-1 production 
      in BEAS-2B cells. Together, the above results illustrate that the activation of 
      p38 MAPK, ERK and JAK-2 but not JNK is crucial for IL-4- and IL-13-induced MCP-1 
      release in human bronchial epithelial cells. Our findings may provide insight 
      into the future development of more effective therapeutic agents for treating 
      allergic asthma.
FAU - Ip, W K
AU  - Ip WK
AD  - Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of 
      Wales Hospital, Shatin, Hong Kong.
FAU - Wong, C K
AU  - Wong CK
FAU - Lam, C W K
AU  - Lam CW
LA  - eng
PT  - Journal Article
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Flavonoids)
RN  - 0 (Imidazoles)
RN  - 0 (Interleukin-13)
RN  - 0 (Interleukins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Pyridines)
RN  - 0 (Tyrphostins)
RN  - 0 (alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide)
RN  - 207137-56-2 (Interleukin-4)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Blotting, Western
MH  - Bronchi/*metabolism
MH  - Cell Line, Transformed
MH  - Cell Survival/drug effects
MH  - Chemokine CCL2/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Epithelial Cells/*metabolism
MH  - Flavonoids/pharmacology
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Interleukin-13/metabolism
MH  - Interleukin-4/metabolism
MH  - Interleukins/*metabolism
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Janus Kinase 2
MH  - *MAP Kinase Signaling System
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/metabolism
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins/antagonists & inhibitors/metabolism
MH  - Pyridines/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tyrphostins/pharmacology
MH  - *Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
PMC - PMC1942012
EDAT- 2006/06/24 09:00
MHDA- 2006/08/08 09:00
PMCR- 2007/07/01
CRDT- 2006/06/24 09:00
PHST- 2006/06/24 09:00 [pubmed]
PHST- 2006/08/08 09:00 [medline]
PHST- 2006/06/24 09:00 [entrez]
PHST- 2007/07/01 00:00 [pmc-release]
AID - CEI3085 [pii]
AID - 10.1111/j.1365-2249.2006.03085.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2006 Jul;145(1):162-72. doi: 10.1111/j.1365-2249.2006.03085.x.