Interaction between cyclooxygenase (COX)-1- and COX-2-products modulates COX-2 expression in the late phase of acute inflammation

• Published in: European journal of pharmacology Vol. 559; no. 2; pp. 210 - 218
• Main Authors: Nakano, Masashi, Denda, Naoyuki, Matsumoto, Misako, Kawamura, Michiko, Kawakubo, Yasuaki, Hatanaka, Ko, Hiramoto, Yoshisuke, Sato, Yu-ichi, Noshiro, Makoto, Harada, Yoshiteru
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 22.03.2007; Elsevier
• Subjects: Acute Disease; Animals; Biological and medical sciences; Blotting, Western; Carrageenan; Carrageenin pleurisy; Cyclooxygenase; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - biosynthesis; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase 2 Inhibitors - therapeutic use; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase Inhibitors - therapeutic use; Dinoprostone - metabolism; Disease Models, Animal; Enzyme Induction - drug effects; Leukocyte transmigration; Lymph Nodes - drug effects; Lymph Nodes - enzymology; Lymph Nodes - metabolism; Lymph Nodes - pathology; Male; Medical sciences; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - metabolism; mPGES-1; Parathymic lymph node; Pharmacology. Drug treatments; Pleural Effusion - chemically induced; Pleural Effusion - drug therapy; Pleural Effusion - enzymology; Pleural Effusion - pathology; Pleurisy - chemically induced; Pleurisy - drug therapy; Pleurisy - enzymology; Pleurisy - pathology; Pneumology; Prostaglandin-E Synthases; Prostaglandin-Endoperoxide Synthases - metabolism; Prostaglandins - metabolism; Rats; Rats, Sprague-Dawley; Respiratory system : syndromes and miscellaneous diseases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Time Factors; Cyclooxygenase; mPGES-1; Leukocyte transmigration; Carrageenin pleurisy; Parathymic lymph node; Prostaglandin-endoperoxide synthase; Late; Lymph node; Respiratory disease; Enzyme; Leukocyte; Acute; Interaction; Cyclooxygenase 1; Inflammation; Pleurisy; Pleural disease; Oxidoreductases
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.11.080

Prostanoid production depends on the activity of two cyclooxygenase (COX) isoforms. It is appreciated that COX-1 plays a role in physiological processes, whereas COX-2 acts in pathological conditions. However their roles, particularly roles of COX-1, have not yet been fully established in inflammation. Here, we examined the effects of COX inhibitors, having differential isoform selectivity, on the late phase of rat carrageenin-induced pleurisy to elucidate the role of COX-2 expressed in the draining lymph nodes and found substantial contribution of COX-1-product(s). Protein and mRNA of COX-2 were detectable with Western blotting analysis and reverse-transcription polymerase chain reaction (RT-PCR) analysis in parathymic lymph nodes, peaking at 48 h after induction of pleurisy. Microsomal prostaglandin E synthase (mPGES)-1 was detectable by immunohistochemical analysis in cells with dendritic processes, a morphological characteristic similar to that of COX-2 expressing cells. Although aspirin, indomethacin and a COX-1 inhibitor, ketorolac, significantly decreased the volume of pleural exudate, they did not affect the levels of COX-2 and mPGES-1 in the lymph node 24 h after induction of pleurisy. In contrast, COX-2 inhibitors, nimesulide and NS-398, had no effect on the exudate volume, but they increased the number of COX-2- and mPGES-1-expressing cells and extension of their dendritic processes with significant increase in the COX-2 level, which were antagonised by ketorolac. These results suggest that COX-2-expressing cells may negatively self-regulate their functions by producing PGE 2 via mPGES-1: migration into the draining lymph node and their differentiation. Moreover, COX-1- and COX-2-derived prostanoids may play differential or sometimes antagonistic roles in the late phase of acute inflammation.