Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The capacity of the skin immune system to mount various types of immune responses is largely dependent on their ability to release and respond to different signals provided by immunoregulatory mediators such as cytokines. There is recent evidence that neuropeptides such as alpha-melanocyte-stimulating hormone (alpha MSH), upon stimulation, are released by epidermal cells including keratinocytes, Langerhans cells, and melanocytes as well as immunocompetent cells. Moreover, alpha MSH recently has been recognized as a potent immunomodulating agent, which inhibits the production and activity of immunoregulatory and proinflammatory cytokines such as IL-1, IL-2, interferon-gamma, downregulates the expression of costimulatory molecules (B7) on antigen-presenting cells; and recently turned out to be a potent inducer of inhibitory mediators such as cytokine synthesis inhibitory factor interleukin-10. Recently, it also was discovered that monocytes among the five known melanocortin (MC) receptors only express MC-1, which is specific for alpha MSH. The expression of MC-1 on monocytes is upregulated by mitogens, endotoxins, and proinflammatory cytokines. There is also recent evidence for the in vivo relevance of the immunosuppressing capacity of alpha MSH. Accordingly, in animals alpha MSH has been shown to inhibit the induction of contact hypersensitivity reactions and to induce hapten-specific tolerance. These findings indicate that, in addition to the cytokine network, neurohormones within the cutaneous microenvironment are a crucial element for the induction, elicitation, and regulation of cutaneous immune and inflammatory responses.
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PMID:Cutaneous immunomodulation and coordination of skin stress responses by alpha-melanocyte-stimulating hormone. 962 65

There is accumulating evidence for a strong interaction between components of the nervous system and the immune system. Accordingly, specific receptors for neuropeptides were found to be expressed on immunocompetent cells and several neuropeptides were recognized as potent regulators of immune and inflammatory reactions. Among various neuropeptides such as substance P, calcitonin gene-related peptide and others alpha-melanocyte-stimulating hormone (alpha-MSH) was found to be produced in the skin. Moreover, melanocortin receptor 1 which is specific for alpha-MSH and ACTH is expressed in the skin on keratinocytes, dendritic cells, macrophages and endothelial cells. In monocytes, macrophages and dendritic cells alpha-MSH inhibits the production and activity of immunoregulatory and proinflammatory cytokines such as IL-2, IFNgamma and IL-1. It downregulates the expression of costimulatory molecules such as CD86 and CD40 and induces the production of suppressor factors such as the cytokine synthesis inhibitory factor IL-10. On endothelial cells alpha-MSH is capable of downregulating the LPS-induced expression of adhesion molecules such as vascular cellular adhesion molecules and E-selectin. Moreover, the LPS-induced activation of transcription factors such as NFkappaB is downregulated by alpha-MSH. In a mouse model intravenous or topical application of alpha-MSH was found to inhibit the induction as well as the effector phase of a contact hypersensitivity reaction and to induce hapten-specific tolerance. Moreover, there is evidence that the N-terminal tripeptide of alpha-MSH is sufficient for its in vitro and in vivo immunomodulatory effects. These findings indicate that the production of immunosuppressing neuropeptides such as alpha-MSH by epidermal cells may play an essential role during the pathogenesis of immune and inflammatory reactions in the skin.
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PMID:alpha-melanocyte-stimulating hormone as a mediator of tolerance induction. 1072 12

Among various neuropeptides such as substance P, calcitonin gene-related peptide and others, alpha-melanocyte-stimulating hormone (alpha-MSH) was found to be produced in the skin. Moreover, melanocortin receptor 1 (MC-1R), which is specific for alpha-MSH and ACTH, is expressed in the skin on keratinocytes, dendritic cells, macrophages and endothelial cells. In monocytes, macrophages and dendritic cells alpha-MSH inhibits the production and activity of immunoregulatory and proinflammatory cytokines such as IL-2, IFN-gamma, TNF-alpha and IL-1. It downregulates the expression of costimulatory molecules such as CD86 and CD40 and induces the production of suppressor factors such as the cytokine synthesis inhibitory factor IL-10. On endothelial cells alpha-MSH is capable of downregulating the LPS-induced expression of adhesion molecules such as vascular cell adhesion molecule (VCAM) and E-selectin. Moreover, the LPS-induced activation of transcription factors such as NF kappa B is downregulated by alpha-MSH. In a mouse model i.v. or topical application of alpha-MSH was found to inhibit the induction phase as well as the effector phase of contact hypersensitivity (CHS) reactions and to induce hapten-specific tolerance. These findings indicate that the production of immunosuppressing neuropeptides such as alpha-MSH by epidermal cells may play an essential role during the pathogenesis of immune and inflammatory reactions in the skin.
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PMID:The role of alpha-MSH as a modulator of cutaneous inflammation. 1126 49