[p38 MAPK/cPLA2 pathway mediates interleukins release in inflammatory cell model].
OBJECTIVE
To explore the underlying mechanism of lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1 beta) and IL-6 release via p38 mitogen-activated protein kinase (MAPK) pathway in HeLa cells for further identification of involved down-stream message factors.


METHODS
HeLa cells were challenged with LPS to reproduce inflammatory cell model. The activity or expression of p38 MAPK, cytosolic phospholipase A(2) (cPLA(2)) and COX-2, was inhibited with pretreatment of inflammatory HeLa cells with the inhibitors (SB203580, AACOCF(3), NS-398) or transfected with the cPLA(2) antisense oligonucleotide (SK7111), then the activities and/or expression of p38 MAPK, cPLA(2), COX-2, and relationship with levels of IL-1 beta and IL-6 supernatants were determined in each group.


RESULTS
SB203580 obviously down-regulated the activities of p38 and cPLA(2), as well as the release of IL-1 beta and IL-6. AACOCF(3) and SK7111 blocked dose-dependently the activity or expression of cPLA(2), IL-1 beta and IL-6 production. However, the expression of COX-2 could hardly be detected in HeLa cells, even after LPS treatment. At the same time, pre-treatment with NS-398 had no effect on IL-1 beta, IL-6 production.


CONCLUSIONS
p38 MAPK/cPLA(2) pathway mediates the expression of IL-1 beta and IL-6 resulting from LPS treatment of HeLa cells, while COX-2, as a down-stream enzyme of cPLA(2) has no effect in this process.
Wang
Xiao-hui
XH
Research Laboratory of Biochemistry, Basic Medical Institute, General Hospital of PLA, Beijing 100853, China.
Yan
Guang-tao
GT
Zhang
Kai
K
Xue
Hui
H
Hao
Xiu-hua
XH
Wang
Lu-huan
LH
D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048051:p38 Mitogen-Activated Protein Kinases; D054510:Phospholipases A2, Cytosolic