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)

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

Opioid-containing immunocytes migrate to inflamed sites where they release beta-endorphin which activates peripheral opioid receptors and produces analgesia. The immigration of immunocytes to sites of inflammation is mediated by adhesion molecules. In this study, the expression of L-, P-, E-selectin and platelet-endothelial adhesion molecule-1 (PECAM-1) in relation to beta-endorphin expression was analyzed by immunohistochemistry in inflamed tissues. The proportion of immunocytes expressing L-selectin was increased in inflamed lymph nodes and subcutaneous paw tissue. P-selectin and PECAM-1 were constitutively expressed on endothelia of noninflamed lymph nodes and subcutaneous tissue and were upregulated in inflammation. beta-endorphin positive cells expressed L-selectin in lymph nodes and subcutaneous tissue. Upregulation of P-selectin and PECAM-1 and the co-localization of L-selectin and beta-endorphin in immunocytes suggest an important role of these adhesion molecules for the recruitment of immunocytes containing beta-endorphin to sites of painful inflammation.
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PMID:Co-expression of beta-endorphin with adhesion molecules in a model of inflammatory pain. 1090 Mar 50

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

The neuroendocrine hormone alpha-melanocyte stimulating hormone (MSH) has profound antiinflammatory and immunomodulating properties. Here we have examined the possibility that alpha-MSH may interfere with the expression and function of cell adhesion molecules (CAMs) expressed by human dermal microvascular endothelial cells (HDMECs) in response to lipopolysaccharide (LPS) or TNFalpha in vitro and in vivo. In HDMEC, alpha-MSH (10(-8)/10(-12) M) profoundly reduced the mRNA and protein expression of E-selectin, vascular CAM (VCAM)-1, and intercellular CAM (ICAM)-1 induced by LPS or TNFalpha as determined by semiquantitative RT-PCR, ELISA, and fluorescence-activated cell sorter analysis. In addition, alpha-MSH significantly impaired the LPS-induced ICAM-1 and VCAM-1-mediated adhesion of lymphocytes to HDMEC monolayer in a functional adhesion assay. Likewise, alpha-MSH effectively inhibited the transcription factor nuclear factor-kappaB activation in HDMEC, which is required for CAM gene expression. Importantly in vivo, in murine LPS-induced cutaneous vasculitis (local Shwartzman reaction), a single ip injection of alpha-MSH significantly suppressed the deleterious vascular damage and hemorrhage by inhibiting the sustained expression of vascular E-selectin and VCAM-1. This persistent expression has been implicated in the dysregulation of diapedesis and activation of leukocytes, which subsequently leads to hemorrhagic vascular damage. Our findings indicate that alpha-MSH may have an important therapeutical potential for the treatment of vasculitis, sepsis, and inflammatory diseases.
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PMID:Alpha-melanocyte stimulating hormone prevents lipopolysaccharide-induced vasculitis by down-regulating endothelial cell adhesion molecule expression. 1248 65

Peripheral corticotropin-releasing hormone (CRH) is an important regulator of localized inflammatory responses. The aim of this study is to define the pathological signaling pathways in which peripheral CRH receptor-mediated responses reside. We report that PECAM-1-expressing synovial membrane endothelial cells are the principal source of CRH receptor subtype 1alpha in chronically inflamed synovial tissue (ST). Analysis of ST from an early arthritis patient cohort (n = 9) established that expression of CRH-R1alpha significantly (P < 0.03) colocalized with PECAM-1 and E-selectin expression in vivo. Freshly excised ST explants released a mediator(s) that acts to promote CRH-R1alpha mRNA to levels present in inflamed human synovium (n = 8). We tested the ability of conditioned medium and individual inflammatory mediators to modulate CRH-R1alpha expression. Histamine selectively induced the expression of CRH-R1alpha, and these effects were mediated through the histamine receptor type 1. Ectopic expression of CRH-R1alpha in normal human endothelial and synoviocyte cells resulted in the induction of the orphan receptor NR4A2 through the reconstitution of cAMP/protein kinase A/cAMP response element-binding protein signaling and identified a role for CRH in modulating nuclear factor kappaB transcriptional activity. CRH enhanced the expression of nitric-oxide synthase (NOS III) to promote NO production from CRH-R1alpha-expressing cells. These data establish a role for CRH receptor-mediated responses in regulating vascular changes associated with chronic synovitis.
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PMID:A role for type 1alpha corticotropin-releasing hormone receptors in mediating local changes in chronically inflamed tissue. 1732 94