The atrial natriuretic peptide regulates the production of inflammatory mediators in macrophages.
The atrial natriuretic peptide (ANP), a member of the natriuretic peptide family, is a cardiovascular hormone which possesses well defined natriuretic, diuretic, and vasodilating properties. Most of the biological effects of ANP aremediated through its guanylyl cyclase coupled A receptor. Because ANP and its receptors have been shown to be expressed and differentially regulated in the immune system, it has been suggested that ANP has an immunomodulatory potency. Much investigation of the effects of ANP on the activation of macrophages has been carried out. ANP was shown to inhibit the lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) in macrophages in an autocrine fashion. ANP in this context was shown to reduce significantly the activation of NF-kappaB and to destabilise iNOS mRNA. ANP, furthermore, can significantly reduce the LPS-induced secretion of tumour necrosis factor alpha (TNFalpha) in macrophages. The relevance of these findings on a regulatory role for ANP on TNFalpha in humans was shown by the fact that ANP significantly reduces the release of TNFalpha in whole human blood. It was furthermore shown to attenuate the release of interleukin 1beta (IL1beta). Interestingly, ANP did not affect the secretion of the anti-inflammatory cytokines IL10 and IL1 receptor antagonist (IL1ra). In summary, ANP was shown to reduce the secretion of inflammatory mediators in macrophages. Therefore, this cardiovascular hormone may possess anti-inflammatory potential.
Kiemer
A K
AK
Department of Pharmacy, Centre of Drug Research, University of Munich, Germany. Alexandra.Kiemer@cup.uni-muenchen.de
Vollmar
A M
AM
D009320:Atrial Natriuretic Factor / Q000502:physiology*; D019898:Autocrine Communication / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D012216:Rheumatic Diseases / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D009320:Atrial Natriuretic Factor; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II