Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation.

Chiao, Hsi; Foster, Steve; Thomas, Robyn; Star, Robert A.

doi:10.1172/jci118639

Cited by 138 publications

(117 citation statements)

References 42 publications

Supporting

Mentioning

109

Contrasting

Order By: Relevance

“…-MSH, an endogenous antiinflammatory cytokine, has been known to reduce cellular infiltrations in various inflammatory conditions such as rat model of arthritis and liver injury from septic shock (20)(21)(22)(23). -MSH also has been reported to have a beneficial effect in ischemia/ reperfusion injury through its inhibitory action on the mouse chemokine KC and ICAM-1 messages and on the induction of iNOS with a resultant decrease in peroxynitrate production (24).…”

Section: Discussionmentioning

confidence: 99%

“…-melanocyte stimulating hormone ( -MSH) is a proopiomelanocortin derivatives and is an endogenous cytokine that suppresses the inflammation in various animal models by way of its inhibitory action on proinflammatory cytokines and chemoattractant chemokines (20)(21)(22)(23) The pathogenesis of chronic cyclosporine A (CsA) nephrotoxicity has not been elucidated, but apoptosis is thought to play an important role in CsA induced tubular atrophy. Recently Fas-Fas ligand system mediated apoptosis has been frequently reported in many epithelial cells as well as in T lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

α-Melanocyte Stimulating Hormone (MSH) decreases cyclosporine A induced apoptosis in cultured human proximal tubular cells

Lee

Han

et al. 2001

J Korean Med Sci

View full text Add to dashboard Cite

The pathogenesis of chronic cyclosporine A (CsA) nephrotoxicity has not been elucidated, but apoptosis is thought to play an important role in CsA induced tubular atrophy. Recently Fas-Fas ligand system mediated apoptosis has been frequently reported in many epithelial cells as well as in T lymphocytes. We investigated the ability of CsA to induce apoptosis in cultured human proximal tubular epithelial cells and also the effect of alpha-MSH on them. Fas, Fas ligand, and an intracellular adaptor protein, Fas-associating protein with death domain (FADD) expression, and poly-ADP ribose polymerase (PARP) cleavage were also studied. CsA induced apoptosis in cultured tubular epithelial cells demonstrated by increased number of TUNEL positive cells and it was accompanied by a significant increase in Fas mRNA and Fas ligand protein expressions. FADD and the cleavage product of PARP also increased, indicating the activation of caspase. In alpha-MSH co-treated cells, apoptosis markedly decreased with downregulation of Fas, Fas ligand and FADD expressions and also the cleavage product of PARP. In conclusion, these data suggest that tubular cell apoptosis mediated by Fas system may play a role in tubular atrophy in chronic CsA nephrotoxicity and pretreatment of alpha-MSH may have a some inhibitory effect on CsA induced tubular cell apoptosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

α-Melanocyte Stimulating Hormone (MSH) decreases cyclosporine A induced apoptosis in cultured human proximal tubular cells

Lee

Han

et al. 2001

J Korean Med Sci

View full text Add to dashboard Cite

show abstract

“…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). The anti-inflammatory effects of ␣-MSH involve a reduction in expression of inflammatory cytokines, including tumor necrosis factor (TNF)-␣, interferon-␥, and interleukin-1, -6, and -8, and inhibition of the inflammatory actions of leukocytes such as neutrophils and macrophages (9,(11)(12)(13).…”

mentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…It is highly likely that the protective effect of leptin is mediated by ␣-MSH, which was shown to protect against endotoxin-induced liver injury and mortality (33,34). The action of ␣-MSH resembles that of glucocorticoids in that it inhibits the production of proinflammatory mediators (33,35).…”

mentioning

confidence: 99%

Leptin Is an Endogenous Protective Protein against the Toxicity Exerted by Tumor Necrosis Factor

Takahashi

1999

Journal of Experimental Medicine

104

101

View full text Add to dashboard Cite

SummaryTumor necrosis factor (TNF) is a central mediator of a number of important pathologies such as the systemic inflammatory response syndrome. Administration of high TNF doses induces acute anorexia, metabolic derangement, inflammation, and eventually shock and death. The in vivo effects of TNF are largely mediated by a complex network of TNF-induced cytokines and hormones acting together or antagonistically. Since TNF also induces leptin, a hormone secreted by adipocytes that modulates food intake and metabolism, we questioned the role of leptin in TNF-induced pathology. To address this question, we tested mouse strains that were defective either in leptin gene ( ob/ob ) or in functional leptin receptor gene ( db/db ), and made use of a receptor antagonist of leptin. Ob/ob and db/db mice, as well as normal mice treated with antagonist, exhibited increased sensitivity to the lethal effect of TNF. Exogenous leptin afforded protection to TNF in ob/ob mice, but failed to enhance the protective effect of endogenous leptin in normal mice. We conclude that leptin is involved in the protective mechanisms that allow an organism to cope with the potentially autoaggressive effects of its immune system.

show abstract

Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation.

Cited by 138 publications

References 42 publications

α-Melanocyte Stimulating Hormone (MSH) decreases cyclosporine A induced apoptosis in cultured human proximal tubular cells

α-Melanocyte Stimulating Hormone (MSH) decreases cyclosporine A induced apoptosis in cultured human proximal tubular cells

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

Leptin Is an Endogenous Protective Protein against the Toxicity Exerted by Tumor Necrosis Factor

Contact Info

Product

Resources

About