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Interleukin‐1 production by mouse macrophages is regulated in a feedback fashion by nitric oxide
Author(s) -
Obermeier Florian,
Gross Volker,
Schölmerich Jürgen,
Falk Werner
Publication year - 1999
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.66.5.829
Subject(s) - nitric oxide , biology , microbiology and biotechnology , macrophage , interleukin , production (economics) , immunology , interleukin 1β , cytokine , biochemistry , in vitro , endocrinology , macroeconomics , economics
The pleiotropic cytokine interleukin‐1 (IL‐1) is an inducer of the inducible nitric oxide synthase (iNOS). It was surprising to find that treatment of normal mice with an iNOS inhibitor resulted in detectable IL‐1β mRNA in colon and spleen, suggesting feedback regulation. When mouse peritoneal exudate cells (PEC) or RAW 264.7 cells were stimulated with lipopolysaccharide (LPS), concomitant inhibition of iNOS resulted in an increase of IL‐1β and IL‐1α protein secretion. Conversely, after addition of the NO‐generating compound NOC‐18, IL‐1β and IL‐1α concentrations in supernatants were dose‐dependently reduced. Co‐stimulation with interferon‐γ (IFN‐γ) reversed the NOC‐18‐mediated suppression of IL‐1α protein concentration into an almost fivefold increase in RAW 264.7 cells. This effect was specific for IL‐1α and was also seen in PEC. The mRNA expression for IL‐1β and IL‐1α in RAW 264.7 cells correlated with the protein levels, suggesting transcriptional regulation by NO. Dysregulated IL‐1/NO cross‐regulation may play a role in inflammatory diseases. J. Leukoc. Biol. 66: 829–836; 1999.