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

Since the first clear demonstration in the 1970s of an immunologic linkage between UV-light exposure of laboratory mice and the development of skin cancers in these animals, much progress has been achieved in our understanding of the effects of UV light on the immune system. At the cellular level, two overlapping mechanisms have been expounded to explain UVB-induced immunosuppression: (1) altered cutaneous antigen presentation due to perturbations in Langerhans' cells and/or the recruitment of macrophage-like cells into skin, and (2) the initiated or up-regulated secretion by skin cells (particularly but not limited to keratinocytes) of soluble mediators of immunosuppression (alpha-melanocyte-stimulating hormone, interleukin 10, tumor necrosis factor alpha). An end result common to both mechanisms is inhibition of Th1-type immunity in favor of preserved or heightened Th2-type immunity. At the molecular level, two targets of UVB radiation are the subject of intense investigation. Circumstantial evidence has accumulated to implicate a direct effect of UVB on DNA (in antigen-presenting cells and/or cytokine-producing cells) as the triggering cause of UVB-evoked immunosuppression. On the other hand, UVB-triggered changes in cell membrane molecules (epidermal growth factor receptor, intercellular adhesion molecule 1, B7) have been correlated with temporally distal UV effects, including the activation of gene transcription pathways and the down-regulation of antigen presentation independent of DNA damage.
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PMID:Basic science answers to questions in clinical contact dermatitis. 879 42

Immune activation of hypothalamic corticotropin-releasing factor (CRF) provides a negative feedback mechanism to modulate peripheral inflammatory responses. We investigated whether central CRF attenuates endothelial expression of intercellular adhesion molecule 1 (ICAM-1) and leukocyte recruitment during endotoxemia in rats and determined its mechanisms of action. As measured by intravital microscopy, lipopolysaccharide (LPS) induced a dose-dependent increase in leukocyte rolling, adhesion, and emigration in mesenteric venules, which was associated with upregulation of endothelial ICAM-1 expression. Intracisternal injection of CRF abrogated both the increased expression of ICAM-1 and leukocyte recruitment. Intravenous injection of the specific CRF receptor antagonist astressin did not modify leukocyte-endothelial cell interactions induced by a high dose of LPS but enhanced leukocyte adhesion induced by a low dose. Blockade of endogenous glucocorticoids but not alpha-melanocyte-stimulating hormone (alpha-MSH) receptors reversed the inhibitory action of CRF on leukocyte-endothelial cell interactions during endotoxemia. In conclusion, cerebral CRF blunts endothelial upregulation of ICAM-1 and attenuates the recruitment of leukocytes during endotoxemia. The anti-inflammatory effects of CRF are mediated by adrenocortical activation and additional mechanisms independent of alpha-MSH.
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PMID:Mechanisms underlying the anti-inflammatory actions of central corticotropin-releasing factor. 1019 46

We have previously shown that alpha-melanocyte-stimulating hormone (alpha-MSH) can oppose tumor necrosis factor alpha activation of NF-kappaB (1-2 h) and intercellular adhesion molecule 1 up-regulation (mRNA by 3 h and protein by 24 h) in melanocytes and melanoma cells. The present study reports on the ability of four MSH peptides to control intracellular peroxide levels and glutathione peroxidase (GPx) activity in pigmentary and nonpigmentary cells. In human HBL melanoma and HaCaT keratinocytes tumor necrosis factor alpha and H(2)O(2) both activated GPx in a time- and concentration-dependent manner (by 30-45 min). alpha-MSH peptides were found to inhibit the stimulated GPx activity and had biphasic dose-response curves. MSH 1-13 and MSH [Nle(4)-d-Phe(7)] achieved maximum inhibition at 10(-10) and 10(-12) m, respectively. Higher concentrations (10-100 fold) of MSH 4-10 and MSH 11-13 were required to produce equivalent levels of inhibition. alpha-MSH was also capable of reducing peroxide accumulation within 15 min, and again this inhibition was biphasic. The data support a role of alpha-MSH in acute protection of cells to oxidative/cytokine action that precedes NF-kappaB and GPx activation. The rapidity and potency of the response to alpha-MSH in pigmentary and nonpigmentary cells suggest this to be a central role of this peptide in cutaneous cells.
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PMID:Alpha-melanocyte-stimulating hormone reduces impact of proinflammatory cytokine and peroxide-generated oxidative stress on keratinocyte and melanoma cell lines. 1082 44

Mesenteric ischemia-reperfusion injury is a serious complication of shock. Because activation of nuclear factor-kappaB (NF-kappaB) has been implicated in this process, we treated rats with vehicle or the IkappaB-alpha inhibitor BAY 11-7085 (25 mg/kg ip) 1 h before mesenteric ischemia-reperfusion (45 min of ischemia followed by reperfusion at 30 min or 6 h) and examined the ileal injury response. Vehicle-treated rats subjected to ischemia-reperfusion exhibited severe mucosal injury, increased myeloperoxidase (MPO) activity, increased expression of interleukin-6 and intercellular adhesion molecule 1 protein, and a biphasic peak of NF-kappaB DNA-binding activity during the 30-min and 6-h reperfusion courses. In contrast, BAY 11-7085-pretreated rats subjected to ischemia-reperfusion exhibited less histological injury and less interleukin-6 and intercellular adhesion molecule 1 protein expression at 30 min of reperfusion but more histological injury at 6 h of reperfusion than vehicle-treated rats subjected to ischemia-reperfusion. Studies with phosphorylation site-specific antibodies demonstrated that IkappaB-alpha phosphorylation at Ser(32),Ser(36) was induced at 30 min of reperfusion, whereas tyrosine phosphorylation of IkappaB-alpha was induced at 6 h of reperfusion. BAY 11-7085 inhibited the former, but not the latter, phosphorylation pathway, whereas alpha-melanocyte-stimulating hormone, which is effective in limiting late ischemia-reperfusion injury to the intestine, inhibited tyrosine phosphorylation of IkappaB-alpha. Thus NF-kappaB appears to play an important role in the generation and resolution of intestinal ischemia-reperfusion injury through different activation pathways.
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PMID:Effects of NF-kappa B inhibition on mesenteric ischemia-reperfusion injury. 1246 47

Alpha-melanocyte stimulating hormone (alpha-MSH) has pigmentary, anti-inflammatory, antipyretic, and general immunomodulatory roles. It can oppose several cytokines including tumor necrosis factor-alpha in a number of tissues, including skin. We have previously shown that alpha-MSH can inhibit tumor necrosis factor-alpha stimulated intercellular adhesion molecule 1 upregulation and nuclear factor kappaB (NFkappaB) transcription factor activation in melanocyte and melanoma cells. It is thought, however, that this MSH biology may also extend to other cells of the skin and in this study we extend our work to keratinocytes. We have investigated in detail the ability of three alpha-MSH peptides to inhibit tumor necrosis factor alpha stimulated NFkappaB activation in nonpigmentary HaCaT keratinocytes (alpha-MSH, L-Lys-L-Pro-L-Val, and L-Lys-L-Pro-D-Val) and two adrenocorticotropic hormone (ACTH) peptides (1-17 and 1-39), reported to be present in skin tissue. NFkappaB/p65 activation was analyzed by electrophoretic mobility shift assay and immunofluorescent microscopy. alpha-MSH, L-Lys-L-Pro-L-Val, and L-Lys-L-Pro-D-Val all significantly inhibited tumor necrosis factor alpha stimulated NFkappaB activation, whereas ACTH 1-17 and 1-39 did not, in the HaCaT keratinocytes. MSH peptides and ACTH 1-39 were effective, however, at inhibiting NFkappaB activation in normal human keratinocytes. Immunolabeling of inhibitor kappaBalpha of NFkappaB (IkappaBalpha) revealed an abnormal localization to the nucleus of HaCaT cells, which was unaffected by MSH/ACTH peptides. In contrast, normal human keratinocytes showed a normal IkappaBalpha distribution that responded to MSH/ACTH with nuclear translocation. Our data support previous work on the role of MSH/ACTH peptides as immunomodulatory/anti-inflammatory regulators, and extend this work to keratinocytes identifying a novel IkappaBalpha mechanism and extends findings to ACTH peptides, identifying an abnormal IkappaBalpha mechanism in the immortal HaCaT versus normal keratinocyte.
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PMID:Inhibition of tumor necrosis factor-alpha stimulated NFkappaB/p65 in human keratinocytes by alpha-melanocyte stimulating hormone and adrenocorticotropic hormone peptides. 1248 24