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. 2001 Nov;60(Suppl 3):iii68–iii70. doi: 10.1136/ard.60.90003.iii68

The atrial natriuretic peptide regulates the production of inflammatory mediators in macrophages

A Kiemer, A Vollmar
PMCID: PMC1766678  PMID: 11890659

Abstract

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 are mediated 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-κB and to destabilise iNOS mRNA. ANP, furthermore, can significantly reduce the LPS-induced secretion of tumour necrosis factor α (TNFα) in macrophages. The relevance of these findings on a regulatory role for ANP on TNFα in humans was shown by the fact that ANP significantly reduces the release of TNFα in whole human blood. It was furthermore shown to attenuate the release of interleukin 1β (IL1β). 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.



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Figure 1  .

Figure 1  

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Natriuretic peptide receptors (NPR). The guanylyl cyclases, NPR-A and NPR-B, contain an extracellular ligand binding domain. NPR-A binds ANP and BNP, whereas NPR-B binds CNP. NPR-C has the potency to internalise and clear the natriuretic peptides and exerts other biological effects by inhibiting the production of cAMP.

Figure 2  .

Figure 2  

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The inhibitory action of ANP on the induction of iNOS. The LPS induction of iNOS is inhibited by ANP through binding to the NPR-A. The inhibitory action involves the destabilisation of iNOS mRNA and inhibition of the activation of NF-κB.

Figure 3  .

Figure 3  

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The inhibitory action of ANP on the induction of TNFα. The LPS-induced expression of TNFα is inhibited by ANP through binding to the NPR-A. The inhibitory action involves transcriptional processes with a reduced activation of NF-κB and AP1.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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