Cyclooxygenase-1 and cyclooxygenase-2 expression in rat kidney and adrenalgland after stimulation with systemic lipopolysaccharide - In situ hybridization and immunocytochemical studies

Cyclooxygenase-2 (COX-2) is a recently discovered isoform of cyclooxygenase that is inducible by various types of inflammatory stimuli. Although this enzyme is considered to play a major role in inflammation processes by cata lyzing the production of prostaglandins, the precise location, distribution , and regulation of prostaglandin synthesis remains unclear in several tiss ues. Using in situ hybridization histochemistry, we investigated the induct ion of COX-1 and COX-2 mRNA expression after systemic administration of a p yrogen, lipopolysaccharide (LPS), in kidney and adrenal gland in the rat. T he COX-2 mRNA signals dramatically increased 1 h after LPS treatment in the kidney outer medulla and adrenal cortex, where almost no or little express ion was observed in nontreated animals, and returned to control levels with in 24 h. COX-2 mRNA levels increased in the kidney inner medulla 6 h after treatment. There was also a significant increase in mRNA levels in the kidn ey cortex and adrenal medulla. On the other hand, COX-1 mRNA levels did not show any detectable changes except in the kidney inner medulla, where a si gnificant downregulation of mRNA expression was observed after LPS treatmen t. Light and electron immune cytochemistry using COX-2 antibodies showed th at strong COX-2 immunoreactivity was localized to certain cortical cells of the thick ascending limb of Henle. Ln addition, based on double-staining w ith antiserum to nitric oxide synthase (NOS) four further cell populations could be identified in kidney cortex, including weakly COX-2-positive, NOS- positive macula densa cells. After LPS treatment, changes in COX-2 immunore activity could be observed in interstitial cells in the kidney medulla and in inner cortical cells in the adrenal gland. These results show that COX-2 is a highly induced enzyme that can be upregulated in specific cell popula tions in kidney and adrenal gland in response to inflammation, leading to t he elevated levels of prostaglandins seen during fever. In contrast COX-1 m RNA levels remained unchanged in this experimental situation, except for a decrease in kidney inner medulla.