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Inhibition of LPS-induced cytokines by Bcl-xL in a murine macrophage cell line.
J Immunol. 2000 Sep 01; 165(5):2729-37.JI

Abstract

The antiapoptotic molecule Bcl-xL has been implicated in the differentiation and survival of activated macrophages in inflammatory conditions. In this report, the role of Bcl-xL in LPS-induced cytokine gene expression and secretion was studied. Bcl-xL-transfected RAW 264 macrophages were protected from gliotoxin-induced apoptosis, indicating the presence of functional Bcl-xL. Overexpression of Bcl-xL in this macrophage cell line was also associated with a marked inhibition of LPS-induced TNF-alpha, JE/monocyte chemoattractant protein 1, and macrophage inflammatory protein 2 secretion. Inhibition of LPS-induced cytokine secretion was paralleled by a decrease in levels of steady-state mRNA for the above cytokines and for IL-1beta. Decreased production of TNF-alpha in Bcl-xL transfectants was not due to increased mRNA degradation, as the mRNA half-lives were the same in Bcl-xL transfectants and control macrophages. Although the composition of NF-kappaB complexes detected by EMSA and supershift analysis in nuclear lysates derived from Bcl-xL transfectants and control cells was indistinguishable, LPS-induced inhibitory kappaBalpha degradation, as well as NF-kappaB binding and AP-1 activation, were slightly decreased by ectopic expression of Bcl-xL. More strikingly, LPS-induced phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase was strongly repressed by Bcl-xL overexpression, offering a possible mechanism for the inhibition of LPS-induced cytokine production. These data provide the first evidence for a novel role for Bcl-xL as an anti-inflammatory mediator in macrophages.

Authors+Show Affiliations

Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10946304

Citation

Lakics, V, et al. "Inhibition of LPS-induced Cytokines By Bcl-xL in a Murine Macrophage Cell Line." Journal of Immunology (Baltimore, Md. : 1950), vol. 165, no. 5, 2000, pp. 2729-37.
Lakics V, Medvedev AE, Okada S, et al. Inhibition of LPS-induced cytokines by Bcl-xL in a murine macrophage cell line. J Immunol. 2000;165(5):2729-37.
Lakics, V., Medvedev, A. E., Okada, S., & Vogel, S. N. (2000). Inhibition of LPS-induced cytokines by Bcl-xL in a murine macrophage cell line. Journal of Immunology (Baltimore, Md. : 1950), 165(5), 2729-37.
Lakics V, et al. Inhibition of LPS-induced Cytokines By Bcl-xL in a Murine Macrophage Cell Line. J Immunol. 2000 Sep 1;165(5):2729-37. PubMed PMID: 10946304.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of LPS-induced cytokines by Bcl-xL in a murine macrophage cell line. AU - Lakics,V, AU - Medvedev,A E, AU - Okada,S, AU - Vogel,S N, PY - 2000/8/18/pubmed PY - 2000/9/23/medline PY - 2000/8/18/entrez SP - 2729 EP - 37 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 165 IS - 5 N2 - The antiapoptotic molecule Bcl-xL has been implicated in the differentiation and survival of activated macrophages in inflammatory conditions. In this report, the role of Bcl-xL in LPS-induced cytokine gene expression and secretion was studied. Bcl-xL-transfected RAW 264 macrophages were protected from gliotoxin-induced apoptosis, indicating the presence of functional Bcl-xL. Overexpression of Bcl-xL in this macrophage cell line was also associated with a marked inhibition of LPS-induced TNF-alpha, JE/monocyte chemoattractant protein 1, and macrophage inflammatory protein 2 secretion. Inhibition of LPS-induced cytokine secretion was paralleled by a decrease in levels of steady-state mRNA for the above cytokines and for IL-1beta. Decreased production of TNF-alpha in Bcl-xL transfectants was not due to increased mRNA degradation, as the mRNA half-lives were the same in Bcl-xL transfectants and control macrophages. Although the composition of NF-kappaB complexes detected by EMSA and supershift analysis in nuclear lysates derived from Bcl-xL transfectants and control cells was indistinguishable, LPS-induced inhibitory kappaBalpha degradation, as well as NF-kappaB binding and AP-1 activation, were slightly decreased by ectopic expression of Bcl-xL. More strikingly, LPS-induced phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase was strongly repressed by Bcl-xL overexpression, offering a possible mechanism for the inhibition of LPS-induced cytokine production. These data provide the first evidence for a novel role for Bcl-xL as an anti-inflammatory mediator in macrophages. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10946304/Inhibition_of_LPS_induced_cytokines_by_Bcl_xL_in_a_murine_macrophage_cell_line_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10946304 DB - PRIME DP - Unbound Medicine ER -