Inhibition of peripheral NF-κB activation by central action of α-melanocyte-stimulating hormone

Ichiyama, Takashi; Sakai, Tetsuhiro; Catania, Anna; Barsh, Gregory S.; Furukawa, Susumu; Lipton, James M.

doi:10.1016/s0165-5728(99)00122-8

Cited by 70 publications

(50 citation statements)

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“…These peptides were equally active in wild-type and recessive yellow (e/e) mice. Another study has reported the anti-inflammatory effect of ␣-MSH in a model of LPS induced brain inflammation in recessive yellow (e/e) mice (9), strongly indicating that involvement of another MC-R also in this experimental condition. Whereas ␣-MSH anti-inflammatory actions have been reported in several studies (13,(25)(26)(27)(28) this is the first study that the nonselective peptide HP228 has been shown to inhibit PMN migration, adding HP288 to the growing list of melanocortins able to down-regulate experimental inflammation.…”

Section: Discussionmentioning

confidence: 84%

“…MC1-R mRNA, but not protein, expression has been found on monocytes, B lymphocytes, NK cells, a subset of cytoxic T cells (4), dendritic cells (5), and more recently mast cells (6). MC1-Rmediated anti-inflammatory effects appear to occur via inhibition of NF-B activation (7,8) and protection of IB␣ degradation (9). These intracellular events would produce a reduction in the expression of proinflammatory cytokines (10) and adhesion molecules (8), thereby affecting the humoral and cellular phases of inflammation (11,12).…”

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confidence: 99%

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Redundancy of a Functional Melanocortin 1 Receptor in the Anti-inflammatory Actions of Melanocortin Peptides: Studies in the Recessive Yellow (e/e) Mouse Suggest an Important Role for Melanocortin 3 Receptor

Getting

Christian

Lam

et al. 2003

The Journal of Immunology

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The issue of which melanocortin receptor (MC-R) is responsible for the anti-inflammatory effects of melanocortin peptides is still a matter of debate. Here we have addressed this aspect using a dual pharmacological and genetic approach, taking advantage of the recent characterization of more selective agonists/antagonists at MC1 and MC3-R as well as of the existence of a naturally defective MC1-R mouse strain, the recessive yellow (e/e) mouse. RT-PCR and ultrastructural analyses showed the presence of MC3-R mRNA and protein in peritoneal macrophages (Mφ) collected from recessive yellow (e/e) mice and wild-type mice. This receptor was functional as Mφ incubation (30 min) with melanocortin peptides led to accumulation of cAMP, an effect abrogated by the MC3/4-R antagonist SHU9119, but not by the selective MC4-R antagonist HS024. In vitro Mφ activation, determined as release of the CXC chemokine KC and IL-1β, was inhibited by the more selective MC3-R agonist γ2-melanocyte stimulating hormone but not by the selective MC1-R agonist MS05. Systemic treatment of mice with a panel of melanocortin peptides inhibited IL-1β release and PMN accumulation elicited by urate crystals in the murine peritoneal cavity. MS05 failed to inhibit any of the inflammatory parameters either in wild-type or recessive yellow (e/e) mice. SHU9119 prevented the inhibitory actions of γ2-melanocyte stimulating hormone both in vitro and in vivo while HS024 was inactive in vivo. In conclusion, agonism at MC3-R expressed on peritoneal Mφ leads to inhibition of experimental nonimmune peritonitis in both wild-type and recessive yellow (e/e) mice.

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Section: Discussionmentioning

confidence: 84%

mentioning

confidence: 99%

Redundancy of a Functional Melanocortin 1 Receptor in the Anti-inflammatory Actions of Melanocortin Peptides: Studies in the Recessive Yellow (e/e) Mouse Suggest an Important Role for Melanocortin 3 Receptor

Getting

Christian

Lam

et al. 2003

The Journal of Immunology

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“…The treatment of mice with α-MSH at the time of haptensensitization causes antigen presenting cells (APC) to prime immunity devoid of a hypersensitivity response (Grabbe et al, 1996). Through melanocortin 1 and melanocortin 3 receptors on macrophages, α-MSH suppresses endotoxin activation of p38 MAPK and NF-κB (Getting et al, 2003;Ichiyama et al, 1999;Yoon et al, 2003). There is a constitutive level of α-MSH in various body tissues and fluids, and in response to a systemic inflammatory response there is an elevation of its concentration in blood (Holdeman et al, 1985;Taylor and Streilein, 1996;Taylor et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages

Taylor

2005

Journal of Neuroimmunology

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Since α-MSH suppresses endotoxin-induced inflammation by innate immunity, it is possible that α-MSH can suppress the interface between innate and adaptive immunity mediated by TLR4-stimulated macrophages. Endotoxin-stimulated macrophages treated with α-MSH are suppressed in nitric oxide and IL-12p70 production, and cannot enhance antigen-stimulated IFN-γ production by Th1 cells. In macrophages treated with α-MSH, the inhibitory molecule IRAK-M is bound to IRAK-1, the proximal intracellular signal molecule of endotoxin-bound TLR4. These results further demonstrate the dynamic contribution of the nervous system, and the role of α-MSH in modulating the innate and adaptive immune interface in an inflammatory response.

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“…and immune activities (1,(3)(4)(5)(6). The anti-inflammatory activity of ␣-MSH has been demonstrated in various disease models including arthritis, septic shock induced by hepatic injury, and endotoxemia/ischemia, suggesting that ␣-MSH is a promising candidate therapeutic drug for inflammatory diseases (7)(8)(9)(10).…”

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confidence: 99%

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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Inhibition of peripheral NF-κB activation by central action of α-melanocyte-stimulating hormone

Cited by 70 publications

References 40 publications

Redundancy of a Functional Melanocortin 1 Receptor in the Anti-inflammatory Actions of Melanocortin Peptides: Studies in the Recessive Yellow (e/e) Mouse Suggest an Important Role for Melanocortin 3 Receptor

Redundancy of a Functional Melanocortin 1 Receptor in the Anti-inflammatory Actions of Melanocortin Peptides: Studies in the Recessive Yellow (e/e) Mouse Suggest an Important Role for Melanocortin 3 Receptor

The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages

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

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