PMID- 12667212
OWN - NLM
STAT- MEDLINE
DCOM- 20030606
LR  - 20190513
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 108
IP  - 4
DP  - 2003 Apr
TI  - The p38 mitogen-activated protein kinase regulates interleukin-1beta-induced IL-8 
      expression via an effect on the IL-8 promoter in intestinal epithelial cells.
PG  - 502-12
AB  - Several lines of evidence implicate the p38 mitogen-activated protein kinase (p38 
      MAPK) in the proinflammatory response to bacterial agents and cytokines. Equally, 
      the transcription factor, nuclear factor (NF)-kappaB, is recognized to be a 
      critical determinant of the inflammatory response in intestinal epithelial cells 
      (IECs). However, the precise inter-relationship between the activation of p38 
      MAPK and activation of the transcription factor NF-kappaB in the intestinal 
      epithelial cell (IEC) system, remains unknown. Here we show that interleukin 
      (IL)-1beta activates all three MAPKs in Caco-2 cells. The production of IL-8 and 
      monocyte chemotactic protein 1 (MCP-1) was attenuated by 50% when these cells 
      were preincubated with the p38 MAPK inhibitor, SB 203580. Further investigation 
      of the NF-kappaB signalling system revealed that the inhibitory effect was 
      independent of the phosphorylation and degradation of IkappaBalpha, the binding 
      partner of NF-kappaB. This effect was also independent of the DNA binding of the 
      p65 Rel A subunit, as well as transactivation, determined by an NF-kappaB 
      luciferase construct, using both SB 203580 and dominant-negative p38 MAPK. 
      Evaluation of IL-8 and MCP-1 RNA messages by reverse transcription-polymerase 
      chain reaction (RT-PCR) revealed that the inhibitory effect of SB 203580 was 
      associated with a reduction in this parameter. Using an IL-8-luciferase promoter 
      construct, an effect of p38 upon its activation by both pharmacological and 
      dominant-negative p38 construct co-transfection was demonstrated. It is concluded 
      that p38 MAPK influences the expression of chemokines in intestinal epithelial 
      cells, through an effect upon the activation of the chemokine promoter, and does 
      not directly involve the activation of the transcription factor NF-kappaB.
FAU - Parhar, Kuljit
AU  - Parhar K
AD  - Department of Medicine, The Jack Bell Research Centre, Vancouver, British 
      Columbia, Canada.
FAU - Ray, Andrew
AU  - Ray A
FAU - Steinbrecher, Urs
AU  - Steinbrecher U
FAU - Nelson, Colleen
AU  - Nelson C
FAU - Salh, Baljinder
AU  - Salh B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Imidazoles)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Pyridines)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Cell Line
MH  - Chemokine CCL2/biosynthesis
MH  - DNA-Binding Proteins/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Epithelial Cells/immunology
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - Imidazoles/pharmacology
MH  - Interleukin-1/*immunology
MH  - Interleukin-8/*biosynthesis
MH  - Intestinal Mucosa/*immunology
MH  - Mitogen-Activated Protein Kinases/antagonists & 
      inhibitors/*immunology/metabolism/physiology
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/metabolism
MH  - Phosphorylation
MH  - Pyridines/pharmacology
MH  - Transcriptional Activation/immunology
MH  - p38 Mitogen-Activated Protein Kinases
PMC - PMC1782920
EDAT- 2003/04/02 05:00
MHDA- 2003/06/07 05:00
PMCR- 2004/04/01
CRDT- 2003/04/02 05:00
PHST- 2003/04/02 05:00 [pubmed]
PHST- 2003/06/07 05:00 [medline]
PHST- 2003/04/02 05:00 [entrez]
PHST- 2004/04/01 00:00 [pmc-release]
AID - 1603 [pii]
AID - 10.1046/j.1365-2567.2003.01603.x [doi]
PST - ppublish
SO  - Immunology. 2003 Apr;108(4):502-12. doi: 10.1046/j.1365-2567.2003.01603.x.