Open AccessGlucocorticoid inhibition of adjuvant arthritis synovial macrophage nitric oxide production: role of lipocortin 1
Author(s) -
Yuan Yang,
Paul Hutchinson,
Leilani Llanes Santos,
Eric Morand
Publication year - 1998
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1998.00438.x
Subject(s) - lipopolysaccharide , medicine , annexin a1 , endocrinology , inflammation , nitric oxide synthase , annexin , nitric oxide , glucocorticoid , macrophage , synovitis , arthritis , chemistry , flow cytometry , biology , immunology , microbiology and biotechnology , biochemistry , in vitro
Nitric oxide (NO) is a mediator of inflammatory injury which is inhibited by glucocorticoids and is implicated in rheumatoid (RA) and adjuvant arthritis (AA). The glucocorticoid‐induced anti‐inflammatory molecule lipocortin 1 is expressed in RA synovium, but the effects of lipocortin 1 on synovial inflammation have been little studied. We investigated the effects of glucocorticoids and lipocortin 1 on inducible NO synthase (iNOS) and glucocorticoids on the induction of lipocortin 1 in AA synovial macrophages. NO production was measured by Griess assay in supernatants of day 14 AA rat synovial explants and of synovial macrophages purified from enzyme‐digested synovium and treated with lipopolysaccharide (LPS) 1 μg/ml, dexamethasone (DEX) 10 −7 M , and anti‐lipocortin 1 MoAb. iNOS and lipocortin 1 expression were detected by flow cytometry using specific MoAb. Cell surface lipocortin was determined by Western blot. NO was produced by all AA synovial explants and NO was released by cultured synovial macrophages (14.5 ± 2.1 μmol/24 h). iNOS was detected in synovial macrophages (ED‐1 + ) by permeabilization flow cytometry. LPS increased synovial macrophage NO release ( P < 0.0001) and iNOS expression ( P = 0.04). DEX inhibited constitutive ( P = 0.002) and LPS‐induced ( P < 0.001) NO release and iNOS expression ( P = 0.03). DEX inhibition of synovial macrophage NO was associated with induction of cell surface and intracellular lipocortin 1. Anti‐lipocortin 1 MoAb treatment reduced the inhibition of NO release by DEX ( P = 0.002), but had no effect on iNOS expression. These findings demonstrate a role for lipocortin 1 in the inhibition by glucocorticoids of AA synovial macrophage iNOS activity.