IL-1beta activates p44/42 and p38 mitogen-activated protein kinases via different pathways in cat esophageal smooth muscle cells.
OBJECTIVE
To examine the pathway related to the IL-1beta-induced activation of mitogen-activated protein (MAP) kinases in cat esophageal smooth muscle cells.


METHODS
Culture of the esophageal smooth muscle cells from cat was prepared. Specific inhibitors were treated before applying the IL-1beta. Western blot analysis was performed to detect the expressions of COX, iNOS and MAP kinases.


RESULTS
In the primary cultured cells, although IL-1beta failed to upregulate the COX and iNOS levels, the levels of the phosphorylated forms of p44/42 MAP kinase and p38 MAP kinase increased in both concentration- and time-dependent manner, of which the level of activation reached a maximum within 3 and 18 h, respectively. The pertussis toxin reduced the level of p44/42 MAP kinase phosphorylation. Tyrphostin 51 and genistein also inhibited this activation. Neomycin decreased the density of the p44/42 MAP kinase band to the basal level. Phosphokinase C (PKC) was found to play a mediating role in the IL-1beta-induced p44/42 MAP kinase activity. In contrast, the activation of p38 MAP kinase was inhibited only by a pretreatment with forskolin, and was unaffected by the other compounds.


CONCLUSIONS
Based on these results, IL-1beta-induced p44/42 MAP kinase activation is mediated by the Gi protein, tyrosine kinase, phospholipase C (PLC) and PKC. The pathway for p38 MAP kinase phosphorylation is different from that of p44/42 MAP kinase, suggesting that it plays a different role in the cellular response to IL-1beta.
Lee
Tai Sang
TS
Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Song
Hyun Ju
HJ
Jeong
Ji Hoon
JH
Min
Young Sil
YS
Shin
Chang Yell
CY
Sohn
Uy Dong
UD
D000818:Animals; D002415:Cats; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004947:Esophagus / Q000187:drug effects* / Q000201:enzymology; D007375:Interleukin-1 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D007375:Interleukin-1; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases