GHS-R1a deficiency mitigates lipopolysaccharide-induced lung injury in mice via the downregulation of macrophage activity

被引：4

作者：

Tanida, Ryota ^{[1
,2
]}

Tsubouchi, Hironobu ^{[1
,3
]}

Yanagi, Shigehisa ^{[1
,3
]}

Saito, Yusuke ^{[4
]}

Toshinai, Koji ^{[5
]}

Miyazaki, Taiga ^{[3
]}

Takamura, Toshinari ^{[2
]}

Nakazato, Masamitsu ^{[1
,6
]}

机构：

[1] Univ Miyazaki, Dept Neurol Respirol Endocrinol & Metab, Internal Med, 5200 Kihara, Kiyotake, Miyazaki 8891692, Japan

[2] Kanazawa Univ, Grad Sch Med Sci, Dept Endocrinol & Metab, Kanazawa, Ishikawa 9208640, Japan

[3] Univ Miyazaki, Fac Med, Dept Internal Med, Div Respirol Rheumatol Infect Dis & Neurol, Kihara 5200, Kiyotake, Miyazaki 8891692, Japan

[4] Univ Miyazaki, Fac Med, Div Pediat, 5200 Kihara, Kiyotake, Miyazaki 8891692, Japan

[5] Shigakkan Univ, Fac Wellness, Dept Sports & Fitness, 55 Nakoyama, Yokone, Obu 4748651, Japan

[6] Univ Miyazaki, Frontier Sci Res Ctr, Div Interorgan Commun Res Project, 5200 Kihara, Kiyotake, Miyazaki 8891692, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2022年 / 589卷

关键词：

ARDS; Inflammation; Ghrelin; Innate immunity; Macrophage; SECRETAGOGUE RECEPTOR; GHRELIN; APOPTOSIS;

D O I：

10.1016/j.bbrc.2021.12.044

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Acute respiratory distress syndrome (ARDS) is a critical illness syndrome characterized by dysregulated pulmonary inflammation. Currently, effective pharmacological treatments for ARDS are unavailable. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHS-R1a), has a pivotal role in regulating energy metabolism and immunomodulation. The role of endogenous ghrelin in ARDS remains unresolved. Herein, we investigated the role of endogenous ghrelin signaling by using GHS-R1a-null (ghsr(-/-)) mice and lipopolysaccharide (LPS)-induced ARDS model. Ghsr(-/-) mice survived longer than controls after LPS-induced lung injury. Ghsr(-/-) mice showed lower levels of pro inflammatory cytokines and higher oxygenation levels after lung injury. The peritoneal macrophages isolated from ghsr(-/-) mice exhibited lower levels of cytokines production and oxygen consumption rate after LPS stimulation. Our results indicated that endogenous ghrelin plays a pivotal role in initiation and continuation in acute inflammatory response in LPS-induced ARDS model by modulating macrophage activity, and highlighted endogenous GHS-R1a signaling in macrophage as a potential therapeutic target in this relentless disease. (c) 2021 Elsevier Inc. All rights reserved.

引用

页码：260 / 266

页数：7

共 23 条

[1] UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals [J].

Andrews, Zane B. ;

Liu, Zhong-Wu ;

Walllingford, Nicholas ;

Erion, Derek M. ;

Borok, Erzsebet ;

Friedman, Jeffery M. ;

Tschop, Matthias H. ;

Shanabrough, Marya ;

Cline, Gary ;

Shulman, Gerald I. ;

Coppola, Anna ;

Gao, Xiao-Bing ;

Horvath, Tamas L. ;

Diano, Sabrina .

NATURE, 2008, 454 (7206) :846-851

[2]

Chen J, 2008, MED SCI MONITOR, V14, pBR141

[3] Understanding NF-κB signaling via mathematical modeling [J].

Cheong, Raymond ;

Hoffmann, Alexander ;

Levchenko, Andre .

MOLECULAR SYSTEMS BIOLOGY, 2008, 4 (1)

[4] Regulation of alveolar macrophage death in acute lung inflammation [J].

Fan, Erica K. Y. ;

Fan, Jie .

RESPIRATORY RESEARCH, 2018, 19

[5] The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material [J].

Ferguson, Niall D. ;

Fan, Eddy ;

Camporota, Luigi ;

Antonelli, Massimo ;

Anzueto, Antonio ;

Beale, Richard ;

Brochard, Laurent ;

Brower, Roy ;

Esteban, Andres ;

Gattinoni, Luciano ;

Rhodes, Andrew ;

Slutsky, Arthur S. ;

Vincent, Jean-Louis ;

Rubenfeld, Gordon D. ;

Thompson, B. Taylor ;

Ranieri, V. Marco .

INTENSIVE CARE MEDICINE, 2012, 38 (10) :1573-1582

[6] Leukocyte elastase induces epithelial apoptosis: role of mitochondial permeability changes and Akt [J].

Ginzberg, HH ;

Shannon, PT ;

Suzuki, T ;

Hong, OY ;

Vachon, E ;

Moraes, T ;

Abreu, MTH ;

Cherepanov, V ;

Wang, XM ;

Chow, CW ;

Downey, GP .

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2004, 287 (01) :G286-G298

[7] GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils [J].

Hattori, N ;

Saito, T ;

Yagyu, T ;

Jiang, BH ;

Kitagawa, K ;

Inagaki, C .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (09) :4284-4291

[8] Pathogenesis of Acute Respiratory Distress Syndrome [J].

Huppert, Laura A. ;

Matthay, Michael A. ;

Ware, Lorraine B. .

SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE, 2019, 40 (01) :31-39

[9] Linking Lipid Metabolism to the Innate Immune Response in Macrophages through Sterol Regulatory Element Binding Protein-1a [J].

Im, Seung-Soon ;

Yousef, Leyla ;

Blaschitz, Christoph ;

Liu, Janet Z. ;

Edwards, Robert A. ;

Young, Stephen G. ;

Raffatellu, Manuela ;

Osborne, Timothy F. .

CELL METABOLISM, 2011, 13 (05) :540-549

[10] Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury [J].

Imai, Yumiko ;

Kuba, Keiji ;

Neely, G. Greg ;

Yaghubian-Malhami, Rubina ;

Perkmann, Thomas ;

van Loo, Geert ;

Ermolaeva, Maria ;

Veldhuizen, Ruud ;

Leung, Y. H. Connie ;

Wang, Hongliang ;

Liu, Haolin ;

Sun, Yang ;

Pasparakis, Manolis ;

Kopf, Manfred ;

Mech, Christin ;

Bavari, Sina ;

Peiris, J. S. Malik ;

Slutsky, Arthur S. ;

Akira, Shizuo ;

Hultqvist, Malin ;

Holmdahl, Rikard ;

Nicholls, John ;

Jiang, Chengyu ;

Binder, Christoph J. ;

Penninger, Josef M. .

CELL, 2008, 133 (02) :235-249

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