Regulation of cyclooxygenase-2 expression in human osteoblastic cells by N-acetylcysteine.
Cyclooxygenase (COX) plays a pivotal role in the inflammatory process of inflammatory arthropathies. Inflammatory cytokines induce COX-2 expression in osteoblasts of inflamed joints, followed by osteoclast activation. The inhibition of COX-2 expression could help prevent prostaglandin E2 secretion, followed by osteoclast activation for bone destruction and resorption. We examined whether the antioxidant N-acetylcysteine (NAC) inhibited COX-2 expression induced in the human osteoblastic cell line MG63 by interleukin-1beta (IL-1beta). According to Western blot and reverse transcription-polymerase chain reaction (RT-PCR) test results, NAC inhibited IL-1beta-induced COX-2 expression in protein and messenger RNA. We also demonstrated immunohistochemically that NAC inhibited NFkappaB nuclear translocation. These results suggested that NAC inhibited both COX-2 expression and NFkappaB nuclear translocation in MG63, which in turn indicated that NAC could inhibit the inflammatory process involved in bone resorption by regulating COX-2 expression at the level of transcription.
Origuchi
T
T
School of Allied Medical Sciences, Nagasaki University, Japan.
Migita
K
K
Nakashima
T
T
Honda
S
S
Yamasaki
S
S
Hida
A
A
Kawakami
A
A
Aoyagi
T
T
Kawabe
Y
Y
Eguchi
K
K
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011817:Rabbits
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000111:Acetylcysteine