Attenuation of extracellular acidic pH-induced cyclooxygenase-2 expression by nitric oxide.
Corneal endothelial cells play an important role in maintaining the transparency and ionic balance of the cornea. Inflammation causes many changes in the intracellular and extracellular environment of the cornea, including acidosis. We examined the relationship between changes in extracellular pH and expression of cyclooxygenase-2 in cultured bovine corneal endothelial cells. When extracellular pH ([pH]o) was reduced to pH 6.4, COX-2 mRNA increased, with a peak at 2 h. This was blocked by pretreatment with actinomycin D and incubation with spermine NONOate (SPER/NO, a nitric oxide donor). Exposure to the H+ ionophore, carbonyl cyanide m-chlorophenylhydrazone (CCCP), also raised COX-2 mRNA levels. CCCP-induced COX-2 mRNA expression was also reduced by SPER/NO. These results were confirmed immuno-cytochemically. These data demonstrate that COX-2 expression is stimulated by the lowering of extracellular pH that could result from bacterial infection, and that this is countered by over-production of nitric oxide, which could also result from bacterial infection.
Cha
Seok Ho
SH
Department of Pharmacology and Toxicology, College of Medicine, Inha University, Incheon 402-751, Korea. shcha@inha.ac.kr
Park
Ji Eun
JE
Kwak
Jin-Oh
JO
Kim
Hyun-Woo
HW
Kim
Jong Bong
JB
Lee
Kwang Youn
KY
Cha
Young-Nam
YN
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D003609:Dactinomycin / Q000494:pharmacology; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000201:enzymology; D006863:Hydrogen-Ion Concentration; D007476:Ionophores / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009589:Nitrogen Oxides; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology
D007476:Ionophores; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; C091861:spermine nitric oxide complex; D003609:Dactinomycin; D013096:Spermine; D009569:Nitric Oxide; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases