Dataset Information

Prostaglandin D production in FM55 melanoma cells is regulated by alpha-melanocyte-stimulating hormone and is not related to melanin production.

ABSTRACT: This study shows that prostaglandins in human FM55 melanoma cells and epidermal melanocytes are produced by COX-1. Prostaglandin production in FM55 melanoma cells was unrelated to that of melanin suggesting that the two processes can occur independently. Alpha-melanocyte-stimulating hormone, which had no effect on melanin production in FM55 cells, stimulated PGD(2) production in these cells without affecting PGE(2). While cAMP pathways may be involved in regulating PGD(2) production, our results suggest that alpha-MSH acts independently of cAMP, possibly by regulating the activity of lipocalin-type PGD synthase. This alpha-MSH-mediated effect may be associated with its role as an immune modulator.

SUBMITTER: Masoodi M

PROVIDER: S-EPMC3068286 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Prostaglandin D production in FM55 melanoma cells is regulated by alpha-melanocyte-stimulating hormone and is not related to melanin production.

Masoodi Mojgan M Nicolaou Anna A Gledhill Karl K Rhodes Lesley E LE Tobin Desmond J DJ Thody Anthony J AJ

Experimental dermatology 20100801 8

This study shows that prostaglandins in human FM55 melanoma cells and epidermal melanocytes are produced by COX-1. Prostaglandin production in FM55 melanoma cells was unrelated to that of melanin suggesting that the two processes can occur independently. Alpha-melanocyte-stimulating hormone, which had no effect on melanin production in FM55 cells, stimulated PGD(2) production in these cells without affecting PGE(2). While cAMP pathways may be involved in regulating PGD(2) production, our results ...[more]

PMID: 20482620

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Project description:ObjectiveDuring infection, metabolism and immunity react dynamically to promote survival through mechanisms that remain unclear. Pro-opiomelanocortin (POMC) cleavage products are produced and released in the brain and in the pituitary gland. One POMC cleavage product, alpha-melanocyte-stimulating hormone (α-MSH), is known to regulate food intake and energy expenditure and has anti-inflammatory effects. However, it is not known whether α-MSH is required to regulate physiological anti-inflammatory responses. We recently developed a novel mouse model with a targeted mutation in Pomc (Pomctm1/tm1 mice) to block production of all α-MSH forms which are required to regulate metabolism. To test whether endogenous α-MSH is required to regulate immune responses, we compared acute bacterial lipopolysaccharide (LPS)-induced inflammation between Pomctm1/tm1 and wild-type Pomcwt/wt mice.MethodsWe challenged 10- to 14-week-old male Pomctm1/tm1 and Pomcwt/wt mice with single i.p. injections of either saline or low-dose LPS (100 μg/kg) and monitored immune and metabolic responses. We used telemetry to measure core body temperature (Tb), ELISA to measure circulating cytokines, corticosterone and α-MSH, and metabolic chambers to measure body weight, food intake, activity, and respiration. We also developed a mass spectrometry method to measure three forms of α-MSH produced in the mouse hypothalamus and pituitary gland.ResultsLPS induced an exaggerated immune response in Pomctm1/tm1 compared to Pomcwt/wt mice. Both groups of mice were hypoactive and hypothermic following LPS administration, but Pomctm1/tm1 mice were significantly more hypothermic compared to control mice injected with LPS. Pomctm1/tm1 mice also had reduced oxygen consumption and impaired metabolic responses to LPS compared to controls. Pomctm1/tm1 mice had increased levels of key proinflammatory cytokines at 2 h and 4 h post LPS injection compared to Pomcwt/wt mice. Lastly, Pomcwt/wt mice injected with LPS compared to saline had increased total α-MSH in circulation 2 h post injection.ConclusionsOur data indicate endogenous α-MSH contributes to the inflammatory immune responses triggered by low-dose LPS administration and suggest that targeting the melanocortin system could be a potential therapeutic for the treatment of sepsis or inflammatory disease.

Dataset Information

Prostaglandin D production in FM55 melanoma cells is regulated by alpha-melanocyte-stimulating hormone and is not related to melanin production.

Publications

Prostaglandin D production in FM55 melanoma cells is regulated by alpha-melanocyte-stimulating hormone and is not related to melanin production.

Similar Datasets

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