α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway Inflammation

Abstract

α-Melanocyte-stimulating hormone (α-MSH) is a neuropeptide controlling melanogenesis in pigmentary cells. In addition, its potent immunomodulatory and immunosuppressive activity has been recently described in cutaneous inflammatory disorders. Whether α-MSH is also produced in the lung and might play a role in the pathogenesis of inflammatory lung conditions, including allergic bronchial asthma, is unknown. Production and functional role of α-MSH were investigated in a murine model of allergic airway inflammation. α-MSH production was detected in bronchoalveolar lavage fluids. Although aerosol challenges stimulate α-MSH production in nonsensitized mice, this rapid and marked stimulation was absent in allergic animals. Treatment of allergic mice with α-MSH resulted in suppression of airway inflammation. These effects were mediated via IL-10 production, because IL-10 knockout mice were resistant to α-MSH treatment. This study provides evidence for a novel function of α-MSH linking neuroimmune functions in allergic airway inflammation.

A role for MC3R in modulating lung inflammation

“…The expression of MC3R on MØ membrane protrusions was confirmed by immuno-gold labelling utilising electron microscopy [14]. Here we have been able to show that alveolar macrophages expressed both MC1R and MC3R, whilst detection of MC1R is in agreement with a previous study [19] the finding of MC3R is novel. The selective MC3R agonist [D-TRP 8 ]-γ-MSH could activate a classical post-receptor signalling in wild-type alveolar MØ, an effect not elicited by the selective MC1R agonist MS05 [14].…”

“…Thus, we cannot rule out an antiinflammatory effect of MS05 in this model, it is highly unlikely since MS05 did not increase cAMP in vitro and has in the past failed to modulate the host inflammatory response. Another potential explanation could be that only 10% of alveolar macrophages express the MC1R [19] and thus their may be insufficient receptors available to elicit a measurable response in this system. The effects observed with the selective MC3R agonist [D-TRP 8 ]-γ-MSH are in contrast to our previous findings indicating a "bell-shaped" response effect with this peptide in peritoneal macrophages elicited from C57 Bl.6 mice [24] and may suggest that alveolar and peritoneal macrophages respond in different ways to melanocortin peptides.…”

“…Melanocortin peptides have long been reported to possess antiinflammatory effects in many experimental models of acute [12][13][14] and chronic inflammation, including inflammatory bowel disease [15], joint arthritis [16,17] and activation and consequent cytokine synthesis within the first few hours of treatment [20,21] and at later time points (>8h) induce the anti-inflammatory protein hemeoxygenase 1 [22] and IL-10 [24]. Only one study has so far addressed the role of α-MSH in modulating eosinophil accumulation levels in a murine model of allergic airway disease [19]: α-MSH treatment of allergic mice led to a significant reduction in inflammation and this protective effect was associated with augmented IL-10 production. The pivotal role of IL-10 was further substantiated using IL-10 null mice where α-MSH was inactive [19].…”

“…Only one study has so far addressed the role of α-MSH in modulating eosinophil accumulation levels in a murine model of allergic airway disease [19]: α-MSH treatment of allergic mice led to a significant reduction in inflammation and this protective effect was associated with augmented IL-10 production. The pivotal role of IL-10 was further substantiated using IL-10 null mice where α-MSH was inactive [19].…”

Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

“…Over the last four decades a substantial body of evidence has exposed their beneficial effects in models of asthma [42][43][44], inflammatory bowel disease [45][46][47], cardiovascular disease [48][49][50][51][52][53], and neuroprotection [54-56] to name just a few areas.…”