Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

alpha-Melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide derived from the proopiomelanocortin by post-translational processing. In addition to its effects on melanocytes, alpha-MSH has potent anti-inflammatory effects when administered systemically or locally. The anti-inflammatory effects of alpha-MSH are mediated by direct effects on cells of the immune system as well as indirectly by affecting the function of resident non-immune cells. alpha-MSH affects several pathways implicated in regulation of inflammatory responses such as NF-kappaB activation, expression of adhesion molecules and chemokine receptors, production of pro-inflammatory cytokines and other mediators. Thus alpha-MSH may modulate inflammatory cell proliferation, activity and migration. The anti-inflammatory effects of alpha-MSH have been confirmed by means of animal models of inflammation such as irritant and allergic contact dermatitis, cutaneous vasculitis, asthma, inflammatory bowel disease, rheumatoid arthritis, ocular and brain inflammation. Most of the anti-inflammatory activities of alpha-MSH can be attributed to its C-terminal tripeptide KPV. K(D)PT, a derivative of KPV corresponding to the amino acid 193-195 of IL-1beta, is currently emerging as another tripeptide with potent anti-inflammatory effects. The anti-inflammatory potential together with the favourable physiochemical properties most likely will allow these agents to be developed for the treatment of inflammatory skin, eye and bowel diseases, allergic asthma and arthritis.
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PMID:alpha-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs. 1793 97

Alpha-MSH is a tridecapeptide derived from proopiomelanocortin. Many studies over the last few years have provided evidence that alpha-MSH has potent protective and antiinflammatory effects. These effects can be elicited via centrally expressed melanocortin receptors that orchestrate descending neurogenic antiinflammatory pathways. alpha-MSH can also exert antiinflammatory and protective effects on cells of the immune system and on peripheral nonimmune cell types expressing melanocortin receptors. At the molecular level, alpha-MSH affects various pathways implicated in regulation of inflammation and protection, i.e., nuclear factor-kappaB activation, expression of adhesion molecules and chemokine receptors, production of proinflammatory cytokines and mediators, IL-10 synthesis, T cell proliferation and activity, inflammatory cell migration, expression of antioxidative enzymes, and apoptosis. The antiinflammatory effects of alpha-MSH have been validated in animal models of experimentally induced fever; irritant and allergic contact dermatitis, vasculitis, and fibrosis; ocular, gastrointestinal, brain, and allergic airway inflammation; and arthritis, but also in models of organ injury. One obstacle limiting the use of alpha-MSH in inflammatory disorders is its pigmentary effect. Due to its preserved antiinflammatory effect but lack of pigmentary action, the C-terminal tripeptide of alpha-MSH, KPV, has been delineated as an alternative for antiinflammatory therapy. KdPT, a derivative of KPV corresponding to amino acids 193-195 of IL-1beta, is also emerging as a tripeptide with antiinflammatory effects. The physiochemical properties and expected low costs of production render both agents suitable for the future treatment of immune-mediated inflammatory skin and bowel disease, fibrosis, allergic and inflammatory lung disease, ocular inflammation, and arthritis.
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PMID:Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. 1861 39