title: Interaction between cyclooxygenase (COX)-1- and COX-2-products modulates COX-2 expression in the late phase of acute inflammation.
abstract: 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 PGE2 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.
authors.affiliation: Department of Mediator and Signal Transduction Pharmacology, Kitasato University Graduate School of Medical Sciences, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakano
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Denda
authors.forename: Misako
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Michiko
authors.initials: M
authors.lastname: Kawamura
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Kawakubo
authors.forename: Ko
authors.initials: K
authors.lastname: Hatanaka
authors.forename: Yoshisuke
authors.initials: Y
authors.lastname: Hiramoto
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Sato
authors.forename: Makoto
authors.initials: M
authors.lastname: Noshiro
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Harada
mesh_terms: D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D002351:Carrageenan; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D008198:Lymph Nodes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010996:Pleural Effusion / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D000071876:Prostaglandin-E Synthases; C497818:Ptges protein, rat; D015232:Dinoprostone