Melanocortin 3 receptor activation with [D-Trp8]-γ-MSH suppresses inflammation in apolipoprotein E deficient mice

Kadiri, James J.; Thapa, Keshav; Kaipio, Katja; Cai, Minying; Hruby, Victor J.; Rinne, Petteri

doi:10.1016/j.ejphar.2020.173186

Cited by 10 publications

(4 citation statements)

References 33 publications

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“…After centrifugation, the cells were resuspended in 300 µL of PBS and samples were pipetted into a flat bottom 96-well plate. As applied previously ( Rinne et al, 2018 ; Viitala et al, 2019 ; Kadiri et al, 2020 ; Kadiri et al, 2021 ; Tadayon et al, 2021 ), samples were analyzed by running 150 µL of each sample with a BD LSR Fortessa™ flow cytometer (BD Biosciences, San Jose, United States) on the same day using BD FACSDiVa v.8 program (BD Biosciences, San Jose, United States). All samples were analyzed by the same person under the same conditions.…”

Section: Methodsmentioning

confidence: 99%

Acute exercise mobilizes CD8+ cytotoxic T cells and NK cells in lymphoma patients

et al. 2023

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Background: Studies have shown that acute exercise can mobilize several leukocyte subpopulations in healthy individuals. Our aim was to investigate whether a 10-min acute exercise has an effect on immune cell proportions in lymphoma patients.Methods: This study included seven lymphoma patients referred to curative oncologic therapy. Three had Hodgkin and four non-Hodgkin lymphoma, one was female, and their mean age was 51. Patients underwent a 10-min acute exercise on a bicycle ergometer at moderate exercise intensity. Whole blood samples were taken at rest, immediately after exercise, and 30 min after exercise. Leukocyte subpopulation levels were determined using flow cytometry.Results: Proportions of total NK cells and CD56+CD16+ NK cells of total leukocytes increased immediately after exercise and decreased back to baseline at 30 min post-exercise. Proportion of CD8+ T cells of total T cells increased and proportion of CD4+ T cells of total T cells decreased immediately after exercise, and both returned to baseline at 30 min post-exercise. There was no change in the proportions of B cells, granulocytes, or monocytes. Exercising diastolic blood pressure correlated positively with changes in total NK cell and CD56+CD16+ NK cell proportions, and exercising mean arterial pressure correlated positively with change in CD56+CD16+ NK cell proportion.Conclusion: Our findings indicate that a single acute exercise bout of only 10 min can cause leukocytosis in lymphoma patients, particularly on cytotoxic T cells and NK cells, which are the most important immune cells fighting against cancer.

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Section: Methodsmentioning

confidence: 99%

Acute exercise mobilizes CD8+ cytotoxic T cells and NK cells in lymphoma patients

et al. 2023

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“…Mice deficient in MC3R after ischemia/reperfusion injury showed increased cell adhesion and emigration as well as increased chemokines [70]. Activating MC3R using the agonist [D-Trp8]-y-MSH in APOE KO mice on a high-fat diet has also been shown to reduce plasma proinflammatory cytokines and leukocytes in both the circulation and in the aorta [71]. However, this intervention model did not result in changes in the expression of aortic adhesion molecules or changes in plaque accumulation and stability [71].…”

Section: Atherosclerosis and The Melanocortinsmentioning

confidence: 99%

Melanocortins and Their Potential for the Treatment, Prevention and Amelioration of Complications of Diabetes

Robinson,

Pickering

2024

Diabetology

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Diabetes mellitus (type I and II) is an advancing global health problem, concerningly increasing in prevalence in most of the developed and developing world. Current therapies, such as the subcutaneous injection of insulin, are invasive and require a close monitoring of blood glucose levels to prevent hypo- or hyperglycaemia from occurring. Despite an inexorable search for a cure since Banting and Best discovered and purified insulin in 1921, insulin remains a solitary insula, still the gold standard for treatment of type I and late-stage type II diabetes mellitus. Apropos of complications, diabetes causes a myriad of secondary maladies, ranging from diabetic kidney disease, diabetic retinopathy and diabetic neuropathy to erectile dysfunction and peripheral vascular disease. While scientists continue to interminably tinker with perfecting mechanical insulin pumps or dampening the immune response to pancreatic beta cells, an important aspect of the aetiology of diabetes should not be neglected, that of the metabolism. At its heart, diabetes can arguably be considered a metabolic disease, and this review suggests a return to focusing on preventing and treating diabetes by focussing on its metabolic causes. This narrative review summarises the potential of a recent class of synthetic peptides, the melanocortins, to help prevent and treat the complications of diabetes mellitus. The review summarises recent work showing the potential benefits of the melanocortins in treating diabetic complications through various pathways.

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“…One of the endogenous pro-resolving pathways that has extensively been studied at the preclinical and clinical levels, and indeed has reached approval for use in humans, is the targeting of the melanocortin pathway ( 13 ). This system comprises a family of five membrane receptors and four endogenous agonists which, among other functions, have demonstrated anti-inflammatory and pro-resolving actions in various models of disease, including arthritis ( 14 – 16 ), gout ( 17 ), intestinal inflammation ( 18 , 19 ), atherosclerosis ( 20 ), uveitis ( 21 ), transplant rejection ( 22 ), or neuroinflammation ( 23 ) among others. Their role in controlling fibroblast activation have also been studied, and this includes in vitro , in vivo , and clinical investigations.…”

Section: Introductionmentioning

confidence: 99%

Melanocortin therapies to resolve fibroblast-mediated diseases

et al. 2023

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Stromal cells have emerged as central drivers in multiple and diverse diseases, and consequently, as potential new cellular targets for the development of novel therapeutic strategies. In this review we revise the main roles of fibroblasts, not only as structural cells but also as players and regulators of immune responses. Important aspects like fibroblast heterogeneity, functional specialization and cellular plasticity are also discussed as well as the implications that these aspects may have in disease and in the design of novel therapeutics. An extensive revision of the actions of fibroblasts on different conditions uncovers the existence of numerous diseases in which this cell type plays a pathogenic role, either due to an exacerbation of their 'structural' side, or a dysregulation of their 'immune side'. In both cases, opportunities for the development of innovative therapeutic approaches exist. In this regard, here we revise the existing evidence pointing at the melanocortin pathway as a potential new strategy for the treatment and management of diseases mediated by aberrantly activated fibroblasts, including scleroderma or rheumatoid arthritis. This evidence derives from studies involving models of in vitro primary fibroblasts, in vivo models of disease as well as ongoing human clinical trials. Melanocortin drugs, which are pro-resolving mediators, have shown ability to reduce collagen deposition, activation of myofibroblasts, reduction of pro-inflammatory mediators and reduced scar formation. Here we also discuss existing challenges, both in approaching fibroblasts as therapeutic targets, and in the development of novel melanocortin drug candidates, that may help advance the field and deliver new medicines for the management of diseases with high medical needs.

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Melanocortin 3 receptor activation with [D-Trp8]-γ-MSH suppresses inflammation in apolipoprotein E deficient mice

Cited by 10 publications

References 33 publications

Acute exercise mobilizes CD8+ cytotoxic T cells and NK cells in lymphoma patients

Acute exercise mobilizes CD8+ cytotoxic T cells and NK cells in lymphoma patients

Melanocortins and Their Potential for the Treatment, Prevention and Amelioration of Complications of Diabetes

Melanocortin therapies to resolve fibroblast-mediated diseases

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