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Double-stranded RNA-induced inducible nitric-oxide synthase expression and interleukin-1 release by murine macrophages requires NF-kappaB activation.
J Biol Chem 1998; 273(24):15301-7JB

Abstract

The effects of double-stranded RNA (synthetic polyinosinic-polycytidylic acid; poly(I-C)) on macrophage expression of inducible nitric-oxide synthase (iNOS), production of nitric oxide, and release of interleukin-1 (IL-1) were investigated. Individually, poly(I-C), interferon-gamma (IFN-gamma), and lipopolysaccharide (LPS) stimulate nitrite production and iNOS expression by RAW 264.7 cells. In combination, the effects of poly(I-C) + IFN-gamma are additive, while poly(I-C) does not further potentiate LPS-induced nitrite production. These results suggest that poly(I-C) and LPS may stimulate iNOS expression by similar signaling pathways, which may be independent of pathways activated by IFN-gamma. LPS-induced iNOS expression is associated with the activation of NF-kappaB. We show that inhibition of NF-kappaB by pyrrolidinedithiocarbamate prevents poly(I-C) + IFN-gamma-, poly(I-C) + LPS-, and LPS-induced iNOS expression, nitrite production and IkappaB degradation by RAW 264.7 cells. The effects of poly(I-C) on iNOS expression appear to be cell-type specific. Poly(I-C), alone or in combination with IFN-gamma, does not stimulate, nor does poly(I-C) potentiate, IL-1-induced nitrite production by rat insulinoma RINm5F cells. In addition, we show that the combination of poly(I-C) + IFN-gamma stimulates iNOS expression, nitrite production, IkappaB degradation, and the release of IL-1 by primary mouse macrophages, and these effects are prevented by pyrrolidinedithiocarbamate. These findings indicate that double-stranded RNA, in the presence of IFN-gamma, is a potent activator of macrophages, stimulating iNOS expression, nitrite production, and IL-1 release by a mechanism which requires the activation of NF-kappaB.

Authors+Show Affiliations

Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri 63104, USA.No 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

9614147

Citation

Heitmeier, M R., et al. "Double-stranded RNA-induced Inducible Nitric-oxide Synthase Expression and Interleukin-1 Release By Murine Macrophages Requires NF-kappaB Activation." The Journal of Biological Chemistry, vol. 273, no. 24, 1998, pp. 15301-7.
Heitmeier MR, Scarim AL, Corbett JA. Double-stranded RNA-induced inducible nitric-oxide synthase expression and interleukin-1 release by murine macrophages requires NF-kappaB activation. J Biol Chem. 1998;273(24):15301-7.
Heitmeier, M. R., Scarim, A. L., & Corbett, J. A. (1998). Double-stranded RNA-induced inducible nitric-oxide synthase expression and interleukin-1 release by murine macrophages requires NF-kappaB activation. The Journal of Biological Chemistry, 273(24), pp. 15301-7.
Heitmeier MR, Scarim AL, Corbett JA. Double-stranded RNA-induced Inducible Nitric-oxide Synthase Expression and Interleukin-1 Release By Murine Macrophages Requires NF-kappaB Activation. J Biol Chem. 1998 Jun 12;273(24):15301-7. PubMed PMID: 9614147.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Double-stranded RNA-induced inducible nitric-oxide synthase expression and interleukin-1 release by murine macrophages requires NF-kappaB activation. AU - Heitmeier,M R, AU - Scarim,A L, AU - Corbett,J A, PY - 1998/6/17/pubmed PY - 1998/6/17/medline PY - 1998/6/17/entrez SP - 15301 EP - 7 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 273 IS - 24 N2 - The effects of double-stranded RNA (synthetic polyinosinic-polycytidylic acid; poly(I-C)) on macrophage expression of inducible nitric-oxide synthase (iNOS), production of nitric oxide, and release of interleukin-1 (IL-1) were investigated. Individually, poly(I-C), interferon-gamma (IFN-gamma), and lipopolysaccharide (LPS) stimulate nitrite production and iNOS expression by RAW 264.7 cells. In combination, the effects of poly(I-C) + IFN-gamma are additive, while poly(I-C) does not further potentiate LPS-induced nitrite production. These results suggest that poly(I-C) and LPS may stimulate iNOS expression by similar signaling pathways, which may be independent of pathways activated by IFN-gamma. LPS-induced iNOS expression is associated with the activation of NF-kappaB. We show that inhibition of NF-kappaB by pyrrolidinedithiocarbamate prevents poly(I-C) + IFN-gamma-, poly(I-C) + LPS-, and LPS-induced iNOS expression, nitrite production and IkappaB degradation by RAW 264.7 cells. The effects of poly(I-C) on iNOS expression appear to be cell-type specific. Poly(I-C), alone or in combination with IFN-gamma, does not stimulate, nor does poly(I-C) potentiate, IL-1-induced nitrite production by rat insulinoma RINm5F cells. In addition, we show that the combination of poly(I-C) + IFN-gamma stimulates iNOS expression, nitrite production, IkappaB degradation, and the release of IL-1 by primary mouse macrophages, and these effects are prevented by pyrrolidinedithiocarbamate. These findings indicate that double-stranded RNA, in the presence of IFN-gamma, is a potent activator of macrophages, stimulating iNOS expression, nitrite production, and IL-1 release by a mechanism which requires the activation of NF-kappaB. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/9614147/Double_stranded_RNA_induced_inducible_nitric_oxide_synthase_expression_and_interleukin_1_release_by_murine_macrophages_requires_NF_kappaB_activation_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=9614147 DB - PRIME DP - Unbound Medicine ER -