PMID- 16054711 OWN - NLM STAT- MEDLINE DCOM- 20060313 LR - 20220409 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1745 IP - 3 DP - 2005 Sep 30 TI - Anisomycin induces COX-2 mRNA expression through p38(MAPK) and CREB independent of small GTPases in intestinal epithelial cells. PG - 393-400 AB - Cyclooxygenase (COX)-2 expression in intestinal epithelial cells is associated with colorectal carcinogenesis. COX-2 expression is induced by numerous growth factors and gastrointestinal hormones through multiple protein kinase cascades. Here, the role of mitogen activated protein kinases (MAPKs) and small GTPases in COX-2 expression was investigated. Anisomycin and sorbitol induced COX-2 expression in non-transformed, intestinal epithelial IEC-18 cells. Both anisomycin and sorbitol activated p38(MAPK) followed by phosphorylation of CREB. SB202190 and PD169316 but neither PD98059 nor U0126 blocked COX-2 expression and CREB phosphorylation by anisomycin or sorbitol. Clostridium difficile toxin B inhibition of small GTPases did not affect anisomycin-induced COX-2 mRNA expression or phosphorylation of p38MAPK and CREB but did inhibit sorbitol-dependent COX-2 expression and phosphorylation of p38MAPK and CREB. Angiotensin (Ang) II-dependent induction of COX-2 mRNA and induced phosphorylation of p38MAPK and CREB were inhibited by toxin B. Reduction of CREB protein in cells transfected with CREB siRNAs inhibited anisomycin-induced COX-2 expression. These results indicate that activation of p38MAPK signaling is sufficient for COX-2 expression in IEC-18 cells. Ang II and sorbitol require small GTPase activity for COX-2 expression via p38MAPK while anisomycin-induced COX-2 expression by p38MAPK does not require small GTPases. This places small GTPase activity down-stream of the AT1 receptor and hyperosmotic stress and up-stream of p38MAPK and CREB. FAU - Shafer, Lindsay M AU - Shafer LM AD - Department of Medicine, David Geffen School of Medicine, CURE: Digestive Diseases Research Center, Jonnson Comprehensive Cancer Center and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1786, USA. FAU - Slice, Lee W AU - Slice LW LA - eng GR - DK061485/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Bacterial Proteins) RN - 0 (Bacterial Toxins) RN - 0 (Butadienes) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (DNA Primers) RN - 0 (Flavonoids) RN - 0 (Imidazoles) RN - 0 (Nitriles) RN - 0 (Pyridines) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (U 0126) RN - 0 (toxB protein, Clostridium difficile) RN - 506T60A25R (Sorbitol) RN - 6C74YM2NGI (Anisomycin) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (Ptgs2 protein, rat) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.6.5.2 (Monomeric GTP-Binding Proteins) RN - GX3Y2V80CV (2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole) RN - PVX798P8GI (4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Animals MH - Anisomycin/*pharmacology MH - Bacterial Proteins/toxicity MH - Bacterial Toxins/toxicity MH - Blotting, Western MH - Butadienes/pharmacology MH - Cyclic AMP Response Element-Binding Protein/genetics/*metabolism MH - Cyclooxygenase 2/*metabolism MH - DNA Primers MH - Flavonoids/pharmacology MH - Gene Expression Regulation/*drug effects MH - Imidazoles/pharmacology MH - Intestinal Mucosa/*metabolism MH - Monomeric GTP-Binding Proteins/antagonists & inhibitors MH - Nitriles/pharmacology MH - Phosphorylation MH - Pyridines/pharmacology MH - RNA Interference MH - RNA, Messenger/*metabolism MH - RNA, Small Interfering/metabolism MH - Rats MH - Signal Transduction/*drug effects MH - Sorbitol/pharmacology MH - p38 Mitogen-Activated Protein Kinases/*metabolism EDAT- 2005/08/02 09:00 MHDA- 2006/03/15 09:00 CRDT- 2005/08/02 09:00 PHST- 2005/04/07 00:00 [received] PHST- 2005/07/01 00:00 [revised] PHST- 2005/07/06 00:00 [accepted] PHST- 2005/08/02 09:00 [pubmed] PHST- 2006/03/15 09:00 [medline] PHST- 2005/08/02 09:00 [entrez] AID - S0167-4889(05)00151-5 [pii] AID - 10.1016/j.bbamcr.2005.07.002 [doi] PST - ppublish SO - Biochim Biophys Acta. 2005 Sep 30;1745(3):393-400. doi: 10.1016/j.bbamcr.2005.07.002.