α-Melanocyte-stimulating Hormone Reduces Impact of Proinflammatory Cytokine and Peroxide-generated Oxidative Stress on Keratinocyte and Melanoma Cell Lines

Haycock, John W.; Rowe, Sarah J.; Cartledge, Susan; Wyatt, Alice; Ghanem, Ghanem; Morandini, Renato; Rennie, I G; MacNeil, Sheila

doi:10.1074/jbc.275.21.15629

Cited by 83 publications

(66 citation statements)

References 50 publications

(34 reference statements)

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“…3A). This biphasic inhibitory effect of ␣-MSH on p38 kinase is consistent with the previous observation that ␣-MSH is most effective at a nanomolar concentration and that its anti-inflammatory effects are biphasic in terms of concentration (20,45).…”

Section: ␣-Msh Inhibits Lps-induced Nf B Activation Via P38supporting

confidence: 78%

α-Melanocyte-stimulating Hormone Inhibits Lipopolysaccharide-induced Tumor Necrosis Factor-α Production in Leukocytes by Modulating Protein Kinase A, p38 Kinase, and Nuclear Factor κB Signaling Pathways

Yoon

Goh

Chun

et al. 2003

Journal of Biological Chemistry

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The neuropeptide ␣-melanocyte-stimulating hormone (␣-MSH) inhibits inflammation by down-regulating the expression of proinflammatory cytokines such as tumor necrosis factor-␣ (TNF-␣) in leukocytes via stimulation of ␣-MSH cell surface receptors. However, the signaling mechanism of ␣-MSH action has not yet been clearly elucidated. Here, we have investigated signaling pathways by which ␣-MSH inhibits lipopolysaccharide (LPS)-induced TNF-␣ production in leukocytes such as THP-1 cells. We focused on the possible roles of protein kinase A (PKA), p38 kinase, and nuclear factor B (NF B) signaling. In THP-1 cells, LPS is known to activate p38 kinase, which in turn activates NF B to induce TNF-␣ production. We found that pretreatment of cells with ␣-MSH blocked LPS-induced p38 kinase and NF B activation as well as TNF-␣ production. This response was proportional to ␣-MSH receptor expression levels, and addition of an ␣-MSH receptor antagonist abolished the inhibitory effects. In addition, ␣-MSH treatment activated PKA, and PKA inhibition abrogated the inhibitory effects of ␣-MSH on p38 kinase activation, NF B activation, and TNF-␣ production. Taken together, our results indicate that stimulation of PKA by ␣-MSH causes inhibition of LPS-induced activation of p38 kinase and NF B to block TNF-␣ production.

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Section: ␣-Msh Inhibits Lps-induced Nf B Activation Via P38supporting

confidence: 78%

α-Melanocyte-stimulating Hormone Inhibits Lipopolysaccharide-induced Tumor Necrosis Factor-α Production in Leukocytes by Modulating Protein Kinase A, p38 Kinase, and Nuclear Factor κB Signaling Pathways

Yoon

Goh

Chun

et al. 2003

Journal of Biological Chemistry

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“…In human diseases, the relationship between concentrations of α-MSH and disease progression in HIV-infection was explored in a prospective study (19). Circulating α-MSH returned to normal levels in patients with sepsis syndrome who recovered and it remained low in those who died (20) As previously reported (23,24), the response to α-MSH was biphasic in inhibitory effects on LPS-induced TNF-α production. One of the possibilities of the reason may be that α-MSH could modulate both inflammatory and antiinflammatory responses regulating intracellular peroxide levels and glutathione peroxidase activity, and an excess dose of α-MSH could break the immunobalance (23).…”

Section: Discussionmentioning

confidence: 65%

Central Neurotranspeptide, Alpha-Melanocyte-Stimulating Hormone (.ALPHA.-MSH) is Upregulated in Patients with Congestive Heart Failure

et al. 2006

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Background α-melanocyte-stimulating hormone (α-MSH), a pro-opiomelanocortin (POMC) derivative, is a neuropeptide with potent anti-inflammatory properties that inhibits tissue injury in a wide array of inflammation models.Objective To determine if α-MSH is involved in the development of congestive heart failure (CHF) with the specific aim of examining its peripheral source and one of the mechanisms. CHF (r=0.41, p<0.0005) Methods The circulating levels of α-MSH were measured in 115 patients with CHF using a doubleantibody radioimmunoassay. To determine one of the sources of circulating α-MSH, human peripheral blood mononuclear cells (PBMC) were stimulated with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α. Furthermore, to clarify one of the functions of α-MSH, PBMC were cultured in the presence or absence of α-MSH. Results Plasma levels of α-MSH were significantly higher in NYHA class II patients with CHF than in control subjects (p<0.0001). A significant correlation was found between the levels of α-MSH and highsensitive testing for C-reactive protein in patients with

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“…The expression of inflammatory cytokines and adhesion receptors such as ICAM-1 are largely under the control of the transcription factor NF-kB (Ghosh et al, 1998). We also found a-MSH to reduce TNF-astimulated NF-kB activity (and oxidative stress) in keratinocyte and melanoma lines (Haycock et al, 1999(Haycock et al, , 2000, suggesting protection of the epidermis from inflammatory and oxidative stresses. In addition, B16 melanoma cells respond to a-MSH with inhibition of growth and reduced adhesion (Robinson and Healy, 2002).…”

mentioning

confidence: 51%

“…a-Melanocyte-simulating hormone can inhibit TNF-a-stimulated NF-kB activity in human melanocytes, melanoma cells and keratinocytes (Haycock et al, 1999(Haycock et al, , 2000Moustafa et al, 2002). In all of these cells, a-MSH inhibited the response to TNF-a by around 50%.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

et al. 2003

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a-Melanocyte stimulating hormone (a-MSH) is known to have pleiotrophic functions including pigmentary, anti-inflammatory, antipyretic and immunoregulatory roles in the mammalian body. It is also reported to influence melanoma invasion with levels of a-, b-and g-MSH correlated clinically with malignant melanoma development, but other studies suggest a-MSH acts to retard invasion. In the present study, we investigated the action of a-MSH on three human melanoma cell lines (HBL, A375-SM and C8161) differing in metastatic potential. a-melanocyte-simulating hormone reduced invasion through fibronectin and also through a human reconstructed skin composite model for the HBL line, and inhibited proinflammatory cytokine-stimulated activation of the NF-kB transcription factor. However, A375-SM and C8161 cells did not respond to a-MSH. Immunofluorescent microscopy and Western blotting identified melanocortin-1 receptor (MC-1R) expression for all three lines and MC-2R on HBL and A375-SM lines. Receptor binding identified a similar affinity for a-MSH for all three lines with the highest number of binding sites on HBL cells. Only the HBL melanoma line demonstrated a detectable cyclic adenosine monophosphate (cAMP) response to a-MSH, although all three lines responded to acute a-MSH addition ( þ (À)-N 6 -(2-phenylisopropyl)-adenosine (PIA)) with an elevation in intracellular calcium. The nonresponsive lines displayed MC-1R polymorphisms (C8161, Arg (wt) 151/Cys 151; A375-SM, homozygous Cys 151), whereas the HBL line was wild type. Stable transfection of the C8161 line with wild-type MC-1R produced cells whose invasion was significantly inhibited by a-MSH. From this data, we conclude that a-MSH can reduce melanoma cell invasion and protect cells against proinflammatory cytokine attack in cells with the wild-type receptor (HBL).

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α-Melanocyte-stimulating Hormone Reduces Impact of Proinflammatory Cytokine and Peroxide-generated Oxidative Stress on Keratinocyte and Melanoma Cell Lines

Cited by 83 publications

References 50 publications

α-Melanocyte-stimulating Hormone Inhibits Lipopolysaccharide-induced Tumor Necrosis Factor-α Production in Leukocytes by Modulating Protein Kinase A, p38 Kinase, and Nuclear Factor κB Signaling Pathways

α-Melanocyte-stimulating Hormone Inhibits Lipopolysaccharide-induced Tumor Necrosis Factor-α Production in Leukocytes by Modulating Protein Kinase A, p38 Kinase, and Nuclear Factor κB Signaling Pathways

Central Neurotranspeptide, Alpha-Melanocyte-Stimulating Hormone (.ALPHA.-MSH) is Upregulated in Patients with Congestive Heart Failure

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

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