Glucocorticoids co-interact with lipoxin A4 via lipoxin A4 receptor (ALX) up-regulation

Biomed Pharmacother. 2007 Jan;61(1):81-5. doi: 10.1016/j.biopha.2006.06.023. Epub 2006 Dec 5.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD11b Antigen / genetics
  • DNA Primers
  • Glucocorticoids / metabolism*
  • Humans
  • Inflammation / physiopathology
  • Lipoxins / metabolism*
  • Neutrophils / drug effects
  • Neutrophils / physiology
  • Receptors, Formyl Peptide / genetics*
  • Receptors, Lipoxin / genetics*
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • CD11b Antigen
  • DNA Primers
  • FPR2 protein, human
  • Glucocorticoids
  • Lipoxins
  • Receptors, Formyl Peptide
  • Receptors, Lipoxin
  • lipoxin A4