The Importance of Melanocortin Receptors and Their Agonists in Pulmonary Disease

Moscowitz, Anna Elizabeth; Asif, Huda; Lindenmaier, Laurence B.; Calzadilla, Andrew; Zhang, Chongxu; Mirsaeidi, Mehdi

doi:10.3389/fmed.2019.00145

Cited by 26 publications

(36 citation statements)

References 72 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As aforementioned, this mutation is linked with obesity in human but equally it has been shown that the interaction between MC3R and its ligand α-melanocyte stimulating hormone (α-MSH) suppressed dermatitis in a mouse model of atopic dermatitis. Even more, α-MSH reduced eosinophil counts, serum levels of IgE, IL-4 and IL-5 in asthmatic mice (10). Their study suggests MC3R activity has an anti-TH2 effect and an abrogation (mutation) of this gene may have caused atopic dermatitis in our patient.…”

Section: Case Reportmentioning

confidence: 53%

A novel insight in the pathophysiology of autoimmune Hepatitis with an Immune activatory mutation in the FLT3 receptor

Arıkan¹

2021

Hepatology Forum

View full text Add to dashboard Cite

Autoimmune hepatitis (AIH) is a chronic progressive autoimmune liver disease characterized by hypergammaglobulinemia, interface hepatitis, female preponderance and presence of autoantibodies in most patients. The presence of HLA-DR3/DR4 and functional impairments in regulatory T cells are associated with AIH. However, AIH is a multifactorial complex disease. In this report, we present a case of a seronegative AIH girl with chronic hepatitis, hyper-IgE, perforating nodular dermatitis and sheer U n c o r r e c t e d P r o o f eosinophilia. To re-evaluate the diagnosis, whole exon sequencing was performed. We determined that the patient has the ancestral haplotype A1-B8-DR3 associated with autoimmunity. More importantly, we found an undocumented point mutation (Ala627Thr) of the FMS-like-tyrosine 3 kinase (FLT3) receptor. This FLT3 receptor gain-of-function mutation is associated with the activation of the mammalian target of rapamycin (mTOR) instigating dendritic cell activation. Furthermore, a loss-of-function mutation in the melanocortin-3 receptor (MC3R) gene paramount in inhibiting IL4 was detected. The constellation of these immune deregulatory factors may have propagated auto-aggression of the liver causing chronic hepatitis with AIH features. Albeit, the seronegativity with eosinophilia and hyper-IgE let us hypothesize that the pathognomonic mechanisms, in this case, diverts from classical AIH pathophysiology. As mTOR is constitutively activated, mTOR inhibitors may be used to treat AIH and dermatitis

show abstract

Section: Case Reportmentioning

confidence: 53%

A novel insight in the pathophysiology of autoimmune Hepatitis with an Immune activatory mutation in the FLT3 receptor

Arıkan¹

2021

Hepatology Forum

View full text Add to dashboard Cite

show abstract

“…Here, we used ACTH to interrogate the role of MCRs in the immune response, as we strove to identify an alternative signaling pathway for the delivery of immunosuppression following heart transplantation. Lymphocytes have been reported to express MC1R, MC3R, and MC5R (26,27,49,(87)(88)(89)(90). However, the expression of MC2R by lymphocytes has not been explored.…”

Section: Discussionmentioning

confidence: 99%

ACTH treatment promotes murine cardiac allograft acceptance

Zhao¹,

Jiang²,

Uehara³

et al. 2021

JCI Insight

View full text Add to dashboard Cite

“…Activation of the melanocortin system with natural or synthetic ligands exerts beneficial effects in acute, chronic, and systemic inflammatory disorders ( 25 – 27 , 48 , 49 , 77 ). Moreover, different clinical studies have investigated efficacy of ACTH and NDP- α -MSH therapies in systemic inflammatory diseases, including ARDS, rheumatoid arthritis, multiple sclerosis (MS), lupus erythematosus (SLE), kidney diseases, and nephrotic syndromes ( 70 – 72 ).…”

Section: The Melanocortin System: a Potent Endogenous Modulatory Pathmentioning

confidence: 99%

“…Melanocortins exert marked anti-inflammatory and immunomodulatory influences. Physiological role and effectiveness in treatment of acute, chronic, and systemic inflammatory disorders are well-documented (25)(26)(27)(28). Exploiting the melanocortin system could form a realistic basis to counteract certain deleterious effects of respiratory viruses not only for the present but also for possible future pandemics.…”

Section: Introductionmentioning

confidence: 99%

Activation of Melanocortin Receptors as a Potential Strategy to Reduce Local and Systemic Reactions Induced by Respiratory Viruses

2020

View full text Add to dashboard Cite

The clinical hallmarks of infections caused by critical respiratory viruses consist of pneumonia, which can progress to acute lung injury (ALI), and systemic manifestations including hypercoagulopathy, vascular dysfunction, and endotheliitis. The disease outcome largely depends on the immune response produced by the host. The bio-molecular mechanisms underlying certain dire consequences of the infection partly arise from an aberrant production of inflammatory molecules, an event denoted as “cytokine storm”. Therefore, in addition to antiviral therapies, molecules able to prevent the injury caused by cytokine excess are under investigation. In this perspective, taking advantage of melanocortin peptides and their receptors, components of an endogenous modulatory system that exerts marked anti-inflammatory and immunomodulatory influences, could be an effective therapeutic strategy to control disease evolution. Exploiting the melanocortin system using natural or synthetic ligands can form a realistic basis to counteract certain deleterious effects of respiratory virus infections. The central and peripheral protective actions exerted following melanocortin receptor activation could allow dampening the harmful events that trigger the cytokine storm and endothelial dysfunction while sustaining the beneficial signals required to elicit repair mechanisms. The long standing evidence for melanocortin safety encourages this approach.

show abstract

The Importance of Melanocortin Receptors and Their Agonists in Pulmonary Disease

Cited by 26 publications

References 72 publications

A novel insight in the pathophysiology of autoimmune Hepatitis with an Immune activatory mutation in the FLT3 receptor

A novel insight in the pathophysiology of autoimmune Hepatitis with an Immune activatory mutation in the FLT3 receptor

ACTH treatment promotes murine cardiac allograft acceptance

Activation of Melanocortin Receptors as a Potential Strategy to Reduce Local and Systemic Reactions Induced by Respiratory Viruses

Contact Info

Product

Resources

About