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N-acetyl cysteine inhibits induction of no production by endotoxin or cytokine stimulated rat peritoneal macrophages, C6 glial cells and astrocytes.
Free Radic Biol Med 1998; 24(1):39-48FR

Abstract

The present study underscores the importance of N-acetyl cysteine (NAC), a potent antioxidant, in inhibiting the induction of NO production by lipopolysaccharides (LPS) and cytokines in peritoneal macrophages, C6 glial cells and primary astrocytes. LPS, interleukin-1 beta (IL-1beta), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) alone or in combinations induced the production of NO to different degrees. NAC when added 2 h earlier to the addition of these stimuli potentially blocked the increase in NO production in macrophages, astrocytes and C6 glial cells. The decrease in NO production by NAC was accompanied by a decrease in inducible nitric oxide synthase (iNOS) activity, in iNOS protein detected by immunoblot analysis with antibodies against iNOS, and in iNOS mRNA determined by reverse-transcriptase coupled polymerase chain reaction (RT-PCR). Time course studies show that inhibition was maximum when NAC was added 2 h prior to the addition of LPS and the degree of inhibition decreased progressively with the increase in time interval when NAC was added after the addition of LPS. In addition to NAC, another antioxidant pyrrolidine dithiocarbamate (PDTC) was also found to inhibit the induction of NO production effectively. Since activation of NF-kappaB is necessary for the induction of iNOS, we examined the effect of NAC on the activation of NF-kappaB. Inhibition of LPS-induced activation of NF-kappaB by NAC in rat peritoneal macrophages suggests that the inhibitory effect of NAC on the induction of iNOS is due to the inhibition of NF-kappaB. Besides NO, NAC also blocked the production of TNF-alpha in rat peritoneal macrophages activated with endotoxin. These results suggest that expression of iNOS and TNF-alpha in macrophages do involve oxygen radicals. The importance of these results in relation to controlling various harmful effects of cytokines released by activated macrophages and glial cells is discussed.

Authors+Show Affiliations

Department of Pediatrics, Medical University of South Carolina, Charleston 29425, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9436612

Citation

Pahan, K, et al. "N-acetyl Cysteine Inhibits Induction of No Production By Endotoxin or Cytokine Stimulated Rat Peritoneal Macrophages, C6 Glial Cells and Astrocytes." Free Radical Biology & Medicine, vol. 24, no. 1, 1998, pp. 39-48.
Pahan K, Sheikh FG, Namboodiri AM, et al. N-acetyl cysteine inhibits induction of no production by endotoxin or cytokine stimulated rat peritoneal macrophages, C6 glial cells and astrocytes. Free Radic Biol Med. 1998;24(1):39-48.
Pahan, K., Sheikh, F. G., Namboodiri, A. M., & Singh, I. (1998). N-acetyl cysteine inhibits induction of no production by endotoxin or cytokine stimulated rat peritoneal macrophages, C6 glial cells and astrocytes. Free Radical Biology & Medicine, 24(1), pp. 39-48.
Pahan K, et al. N-acetyl Cysteine Inhibits Induction of No Production By Endotoxin or Cytokine Stimulated Rat Peritoneal Macrophages, C6 Glial Cells and Astrocytes. Free Radic Biol Med. 1998 Jan 1;24(1):39-48. PubMed PMID: 9436612.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - N-acetyl cysteine inhibits induction of no production by endotoxin or cytokine stimulated rat peritoneal macrophages, C6 glial cells and astrocytes. AU - Pahan,K, AU - Sheikh,F G, AU - Namboodiri,A M, AU - Singh,I, PY - 1998/1/22/pubmed PY - 1998/1/22/medline PY - 1998/1/22/entrez SP - 39 EP - 48 JF - Free radical biology & medicine JO - Free Radic. Biol. Med. VL - 24 IS - 1 N2 - The present study underscores the importance of N-acetyl cysteine (NAC), a potent antioxidant, in inhibiting the induction of NO production by lipopolysaccharides (LPS) and cytokines in peritoneal macrophages, C6 glial cells and primary astrocytes. LPS, interleukin-1 beta (IL-1beta), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) alone or in combinations induced the production of NO to different degrees. NAC when added 2 h earlier to the addition of these stimuli potentially blocked the increase in NO production in macrophages, astrocytes and C6 glial cells. The decrease in NO production by NAC was accompanied by a decrease in inducible nitric oxide synthase (iNOS) activity, in iNOS protein detected by immunoblot analysis with antibodies against iNOS, and in iNOS mRNA determined by reverse-transcriptase coupled polymerase chain reaction (RT-PCR). Time course studies show that inhibition was maximum when NAC was added 2 h prior to the addition of LPS and the degree of inhibition decreased progressively with the increase in time interval when NAC was added after the addition of LPS. In addition to NAC, another antioxidant pyrrolidine dithiocarbamate (PDTC) was also found to inhibit the induction of NO production effectively. Since activation of NF-kappaB is necessary for the induction of iNOS, we examined the effect of NAC on the activation of NF-kappaB. Inhibition of LPS-induced activation of NF-kappaB by NAC in rat peritoneal macrophages suggests that the inhibitory effect of NAC on the induction of iNOS is due to the inhibition of NF-kappaB. Besides NO, NAC also blocked the production of TNF-alpha in rat peritoneal macrophages activated with endotoxin. These results suggest that expression of iNOS and TNF-alpha in macrophages do involve oxygen radicals. The importance of these results in relation to controlling various harmful effects of cytokines released by activated macrophages and glial cells is discussed. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/9436612/N_acetyl_cysteine_inhibits_induction_of_no_production_by_endotoxin_or_cytokine_stimulated_rat_peritoneal_macrophages_C6_glial_cells_and_astrocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(97)00137-8 DB - PRIME DP - Unbound Medicine ER -