Premium
Mechanism of suppression of nitric oxide synthase expression by interleukin‐4 in primary mouse macrophages
Author(s) -
Bogdan Christian,
Vodovotz Yoram,
Paik John,
Xie Qiaowen,
Nathan Carl
Publication year - 1994
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.55.2.227
Subject(s) - nitric oxide synthase , nitric oxide , lipopolysaccharide , biology , stimulation , macrophage , tumor necrosis factor alpha , cytokine , interleukin , immunology , secretion , microbiology and biotechnology , endocrinology , in vitro , biochemistry
Abstract Nitric oxide (NO) contributes to the anti‐tumor, antimicrobial, and immunosuppressive activity of macrophages. An inducible form of NO synthase (iNOS) is responsible for high output generation of nitric oxide by macrophages after stimulation with cytokines and/or lipopolysaccharide (LPS). In the present study, we demonstrate that interleukin 4 (IL‐4) suppressed production of NO by primary mouse peritoneal macrophages exposed to IFN‐ γ with or without LPS, even while synergizing with IFN‐ γ to increase the secretion of TNF‐α. Suppression of NO production was paralleled by decreases in iNOS enzyme activity and iNOS antigen. IL‐4 did not inhibit induction of iNOS mRNA 4–6 h after exposure to IFN‐ γ , but strongly reduced iNOS mRNA at later times of stimulation (24–72 h), without increasing its turnover. The conditions for maximal suppression of iNOS expression by IL‐4 and the mechanisms of suppression differed from those determined in parallel for transforming growth‐factor‐ β as described elsewhere. These results illustrate the diversity of phenotypes of macrophages deactivated by different cytokines, and demonstrate that IL‐4 has the potential to reduce one component of the anti‐tumor, antimicrobial, and immunosuppressive activities of macrophages. J. Leukoc. Biol. 55: 227–233; 1994.