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Acetaminophen inhibits iNOS gene expression in RAW 264.7 macrophages: differential regulation of NF-kappaB by acetaminophen and salicylates.
Biochem Biophys Res Commun 2000; 272(3):758-64BB

Abstract

Acetaminophen is a widely used analgesic and anti-inflammatory drug that is considered a good alternative to salicylates for individuals who cannot tolerate salicylates. Nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation. Recent evidence suggests that anti-inflammatory effect of salicylates lies in the inhibition of iNOS, but nothing has been reported about the direct effect of iNOS expression by acetaminophen. The present study was designed to elucidate sequentially the action mechanisms of acetaminophen and salicylates (aspirin and sodium salicylate) on lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)-induced iNOS expression in RAW 264.7 macrophages. Both acetaminophen and salicylates inhibited NO production and iNOS protein expression in a dose dependent manner. Acetaminophen inhibited iNOS mRNA expression, promoter activity of iNOS gene and nuclear factor-kappa B (NF-kappaB) binding activity induced by LPS plus IFN-gamma, whereas salicylates did not show any effect on them. In addition, salicylates did not affect on iNOS mRNA stability induced by LPS plus IFN-gamma. Furthermore, the inhibition of iNOS protein expression and NO production by salicylates was disappeared when salicylates were added for only 5 h to inhibit the early event of iNOS expression. Aspirin also dose dependently inhibited iNOS enzyme activity in cell-free extracts, whereas no significant differences were observed in extracts treated with sodium salicylate or acetaminophen. These findings suggest that acetaminophen may exert analgesic or anti-inflammatory effect by inhibiting iNOS expression induced by LPS plus IFN-gamma at transcriptional level by suppression of NF-kappaB binding activity, whereas salicylates exert its effect by inhibiting iNOS expression at the translational or posttranslational level.

Authors+Show Affiliations

Department of Pharmacology, Chungnam National University, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

10860828

Citation

Ryu, Y S., et al. "Acetaminophen Inhibits iNOS Gene Expression in RAW 264.7 Macrophages: Differential Regulation of NF-kappaB By Acetaminophen and Salicylates." Biochemical and Biophysical Research Communications, vol. 272, no. 3, 2000, pp. 758-64.
Ryu YS, Lee JH, Seok JH, et al. Acetaminophen inhibits iNOS gene expression in RAW 264.7 macrophages: differential regulation of NF-kappaB by acetaminophen and salicylates. Biochem Biophys Res Commun. 2000;272(3):758-64.
Ryu, Y. S., Lee, J. H., Seok, J. H., Hong, J. H., Lee, Y. S., Lim, J. H., ... Hur, G. M. (2000). Acetaminophen inhibits iNOS gene expression in RAW 264.7 macrophages: differential regulation of NF-kappaB by acetaminophen and salicylates. Biochemical and Biophysical Research Communications, 272(3), pp. 758-64.
Ryu YS, et al. Acetaminophen Inhibits iNOS Gene Expression in RAW 264.7 Macrophages: Differential Regulation of NF-kappaB By Acetaminophen and Salicylates. Biochem Biophys Res Commun. 2000 Jun 16;272(3):758-64. PubMed PMID: 10860828.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acetaminophen inhibits iNOS gene expression in RAW 264.7 macrophages: differential regulation of NF-kappaB by acetaminophen and salicylates. AU - Ryu,Y S, AU - Lee,J H, AU - Seok,J H, AU - Hong,J H, AU - Lee,Y S, AU - Lim,J H, AU - Kim,Y M, AU - Hur,G M, PY - 2000/6/22/pubmed PY - 2000/6/22/medline PY - 2000/6/22/entrez SP - 758 EP - 64 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 272 IS - 3 N2 - Acetaminophen is a widely used analgesic and anti-inflammatory drug that is considered a good alternative to salicylates for individuals who cannot tolerate salicylates. Nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation. Recent evidence suggests that anti-inflammatory effect of salicylates lies in the inhibition of iNOS, but nothing has been reported about the direct effect of iNOS expression by acetaminophen. The present study was designed to elucidate sequentially the action mechanisms of acetaminophen and salicylates (aspirin and sodium salicylate) on lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)-induced iNOS expression in RAW 264.7 macrophages. Both acetaminophen and salicylates inhibited NO production and iNOS protein expression in a dose dependent manner. Acetaminophen inhibited iNOS mRNA expression, promoter activity of iNOS gene and nuclear factor-kappa B (NF-kappaB) binding activity induced by LPS plus IFN-gamma, whereas salicylates did not show any effect on them. In addition, salicylates did not affect on iNOS mRNA stability induced by LPS plus IFN-gamma. Furthermore, the inhibition of iNOS protein expression and NO production by salicylates was disappeared when salicylates were added for only 5 h to inhibit the early event of iNOS expression. Aspirin also dose dependently inhibited iNOS enzyme activity in cell-free extracts, whereas no significant differences were observed in extracts treated with sodium salicylate or acetaminophen. These findings suggest that acetaminophen may exert analgesic or anti-inflammatory effect by inhibiting iNOS expression induced by LPS plus IFN-gamma at transcriptional level by suppression of NF-kappaB binding activity, whereas salicylates exert its effect by inhibiting iNOS expression at the translational or posttranslational level. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/10860828/Acetaminophen_inhibits_iNOS_gene_expression_in_RAW_264_7_macrophages:_differential_regulation_of_NF_kappaB_by_acetaminophen_and_salicylates_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(00)92863-8 DB - PRIME DP - Unbound Medicine ER -