Glucocorticoids co-interact with lipoxin A4 via lipoxin A4 receptor (ALX) up-regulation.
Lipoxin A(4) (LXA(4)) is an eicosanoid which is produced via lipoxygenases and characteristic of its anti-inflammatory effect in many metabolites of arachidonic acid, which are mostly pro-inflammatory. Glucocorticoids are well known also for their strong anti-inflammatory action but induce 5-lipoxygenase, essential to synthesize leukotrienes, which are pro-inflammatory. To elucidate the interaction of glucocorticoids and lipoxin A(4) for anti-inflammation, we analyzed in vitro expression of lipoxin A(4) receptor (ALX) on human neutrophils and the in vivo anti-inflammatory effect of glucocorticoids and LXA(4) using a dermal inflammation mouse model. ALX mRNA was up-regulated by dexamethasone (Dex) in human neutrophils. A glucocorticoid receptor antagonist, mifepristone, suppressed up-regulation of ALX induced by Dex. LXA(4) and/or Dex decreased CD11b expression on human neutrophils and suppressed mouse dermatitis induced by LTB(4). These results suggest that anti-inflammatory effects of glucocorticoids depend at least partly on up-regulation of ALX and that the lipoxin system could be a negative feedback regulator for LTB(4).
Hashimoto
Atsushi
A
Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Murakami
Yousuke
Y
Kitasato
Hidero
H
Hayashi
Izumi
I
Endo
Hirahito
H
D000328:Adult; D039481:CD11b Antigen / Q000235:genetics; D017931:DNA Primers; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D044045:Lipoxins / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D044042:Receptors, Formyl Peptide / Q000235:genetics*; D044067:Receptors, Lipoxin / Q000235:genetics*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D039481:CD11b Antigen; D017931:DNA Primers; C105101:FPR2 protein, human; D005938:Glucocorticoids; D044045:Lipoxins; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C040527:lipoxin A4