Attenuation of Extracellular Acidic pH-induced Cyclooxygenase-2 Expression by Nitric Oxide

  • Cha, Seok Ho (Department of Pharmacology and Toxicology, College of Medicine, Inha University) ;
  • Park, Ji Eun (Department of Biology, Catholic University of Daegu) ;
  • Kwak, Jin-Oh (Department of Pharmacology and Toxicology, College of Medicine, Inha University) ;
  • Kim, Hyun-Woo (Department of Pharmacology and Toxicology, College of Medicine, Inha University) ;
  • Kim, Jong Bong (Department of Biology, Catholic University of Daegu) ;
  • Lee, Kwang Youn (Department of Pharmacology, College of Medicine, Yeungnam University) ;
  • Cha, Young-Nam (Department of Pharmacology and Toxicology, College of Medicine, Inha University)
  • Received : 2004.11.05
  • Accepted : 2004.12.28
  • Published : 2005.04.30

Abstract

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.

Acknowledgement

Supported by : Inha University

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