دورية أكاديمية
أعرض في EDS

Alpha-melanocyte-stimulating hormone contributes to an anti-inflammatory response to lipopolysaccharide.

التفاصيل البيبلوغرافية
العنوان: Alpha-melanocyte-stimulating hormone contributes to an anti-inflammatory response to lipopolysaccharide.
المؤلفون: Reynolds RP; Department of Internal Medicine, Center for Hypothalamic Research, Dallas, TX, USA., Fan RR; Department of Internal Medicine, Center for Hypothalamic Research, Dallas, TX, USA., Tinajero A; Department of Internal Medicine, Center for Hypothalamic Research, Dallas, TX, USA., Luo X; Department of Biochemistry, Dallas, TX, USA., Huen SC; Department of Internal Medicine (Nephrology) and Pharmacology, Dallas, TX, USA., Fujikawa T; Department of Internal Medicine, Center for Hypothalamic Research, Dallas, TX, USA; The Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA., Lee S; Department of Internal Medicine, Center for Hypothalamic Research, Dallas, TX, USA., Lemoff A; Department of Biochemistry, Dallas, TX, USA., Mountjoy KG; Department of Molecular Medicine and Pathology, University of Auckland, Private Bag 92019, Auckland 1043, New Zealand., Elmquist JK; Department of Internal Medicine, Center for Hypothalamic Research, Dallas, TX, USA; The Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: Joel.Elmquist@utsouthwestern.edu.
المصدر: Molecular metabolism [Mol Metab] 2024 Sep; Vol. 87, pp. 101986. Date of Electronic Publication: 2024 Jul 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier GmbH Country of Publication: Germany NLM ID: 101605730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2212-8778 (Electronic) Linking ISSN: 22128778 NLM ISO Abbreviation: Mol Metab Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [München] : Elsevier GmbH, 2012-
مواضيع طبية MeSH: alpha-MSH*/metabolism , alpha-MSH*/pharmacology , Lipopolysaccharides*/pharmacology , Pro-Opiomelanocortin*/metabolism , Inflammation*/metabolism, Animals ; Mice ; Male ; Mice, Inbred C57BL ; Corticosterone/metabolism ; Corticosterone/blood
مستخلص: Objective: During infection, metabolism and immunity react dynamically to promote survival through mechanisms that remain unclear. Pro-opiomelanocortin (POMC) cleavage products are produced and released in the brain and in the pituitary gland. One POMC cleavage product, alpha-melanocyte-stimulating hormone (α-MSH), is known to regulate food intake and energy expenditure and has anti-inflammatory effects. However, it is not known whether α-MSH is required to regulate physiological anti-inflammatory responses. We recently developed a novel mouse model with a targeted mutation in Pomc (Pomc tm1/tm1 mice) to block production of all α-MSH forms which are required to regulate metabolism. To test whether endogenous α-MSH is required to regulate immune responses, we compared acute bacterial lipopolysaccharide (LPS)-induced inflammation between Pomc tm1/tm1 and wild-type Pomc wt/wt mice.
Methods: We challenged 10- to 14-week-old male Pomc tm1/tm1 and Pomc wt/wt mice with single i.p. injections of either saline or low-dose LPS (100 μg/kg) and monitored immune and metabolic responses. We used telemetry to measure core body temperature (T b ), ELISA to measure circulating cytokines, corticosterone and α-MSH, and metabolic chambers to measure body weight, food intake, activity, and respiration. We also developed a mass spectrometry method to measure three forms of α-MSH produced in the mouse hypothalamus and pituitary gland.
Results: LPS induced an exaggerated immune response in Pomc tm1/tm1 compared to Pomc wt/wt mice. Both groups of mice were hypoactive and hypothermic following LPS administration, but Pomc tm1/tm1 mice were significantly more hypothermic compared to control mice injected with LPS. Pomc tm1/tm1 mice also had reduced oxygen consumption and impaired metabolic responses to LPS compared to controls. Pomc tm1/tm1 mice had increased levels of key proinflammatory cytokines at 2 h and 4 h post LPS injection compared to Pomc wt/wt mice. Lastly, Pomc wt/wt mice injected with LPS compared to saline had increased total α-MSH in circulation 2 h post injection.
Conclusions: Our data indicate endogenous α-MSH contributes to the inflammatory immune responses triggered by low-dose LPS administration and suggest that targeting the melanocortin system could be a potential therapeutic for the treatment of sepsis or inflammatory disease.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)
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معلومات مُعتمدة: T32 HL139438 United States HL NHLBI NIH HHS; R01 DK118725 United States DK NIDDK NIH HHS; P01 DK119130 United States DK NIDDK NIH HHS; R35 GM137984 United States GM NIGMS NIH HHS; R01 DK127274 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: LPS; Mouse model; POMC; Thermogenesis; α-MSH
المشرفين على المادة: 581-05-5 (alpha-MSH)
0 (Lipopolysaccharides)
66796-54-1 (Pro-Opiomelanocortin)
W980KJ009P (Corticosterone)
تواريخ الأحداث: Date Created: 20240711 Date Completed: 20240805 Latest Revision: 20240902
رمز التحديث: 20240902
مُعرف محوري في PubMed: PMC11362619
DOI: 10.1016/j.molmet.2024.101986
PMID: 38992428
قاعدة البيانات: MEDLINE
الوصف
تدمد:2212-8778
DOI:10.1016/j.molmet.2024.101986