Proinflammatory cytokines induce cyclooxygenase-2 mRNA and protein expression in human pulp cell cultures.
The increased release of prostaglandins (PG) within pulpal tissues is considered to play a pathogenic role during pulpal disease progression. The rate-limiting step in the formation of PG from arachidonic acid is catalyzed by cyclooxygenase (COX). COX-2 is an inducible enzyme believed to be responsible for PG synthesis at site of inflammation. The effect of proinflammatory cytokines on human pulp cells with special reference to COX-2 expression has not been reported earlier. The aim of the present study was to investigate the effects of interleukin (IL)-1alpha and tumor necrosis factor-alpha (TNF-alpha) on the expression of COX-2 mRNA gene and protein in cultured human pulp cells. Investigations of the time dependence of COX-2 mRNA expression in proinflammatory cytokines-treated human pulp cells revealed a rapid accumulation of the transcript, a significant signal first detectable 1 h after exposure. In addition, both IL-1alpha and TNF-alpha up-regulated COX-2 protein expression by human pulp cells. The kinetics of this response showed that COX-2 was detectable in cell lysates as early as 2 h post proinflammatory cytokines challenge and remained elevated throughout the 24-h incubation period. This suggests that one of the pathogenic mechanisms of pulpal inflammation in vivo may be the synthesis of COX-2 by resident cells in response to a proinflammatory cytokines challenge. COX-2 may play an important role in the regulation of prostanoid formation in the pathogenesis of pulpal inflammation. Taken together, we propose that the use of selective COX-2 inhibitors might provide a valuable tool in the control of pulpal inflammation.
Chang
Yu-Chao
YC
Institute of Stomatology, Chung Shan Medical University Hospital, Taichung, Taiwan.
Yang
Shun-Fa
SF
Huang
Fu-Mei
FM
Liu
Chia-Ming
CM
Tai
Kuo-Wei
KW
Hsieh
Yih-Shou
YS
D018929:Cell Culture Techniques; D051546:Cyclooxygenase 2; D003782:Dental Pulp / Q000187:drug effects* / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects* / Q000235:genetics; D008565:Membrane Proteins; D010544:Peroxidases / Q000187:drug effects* / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000235:genetics; D011671:Pulpitis / Q000201:enzymology / Q000209:etiology; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
D018836:Inflammation Mediators; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010544:Peroxidases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases