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

Ryota Tanida; Hironobu Tsubouchi; Shigehisa Yanagi; Yusuke Saito; Koji Toshinai; Taiga Miyazaki; Toshinari Takamura; Masamitsu Nakazato

doi:10.1016/j.bbrc.2021.12.044

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

Biochem Biophys Res Commun. 2022 Jan 22:589:260-266. doi: 10.1016/j.bbrc.2021.12.044. Epub 2021 Dec 15.

Authors

Ryota Tanida¹, Hironobu Tsubouchi², Shigehisa Yanagi³, Yusuke Saito⁴, Koji Toshinai⁵, Taiga Miyazaki⁶, Toshinari Takamura⁷, Masamitsu Nakazato⁸

Affiliations

¹ Department of Neurology, Respirology, Endocrinology and Metabolism, Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan; Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, 920-8640, Japan.
² Department of Neurology, Respirology, Endocrinology and Metabolism, Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan; Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki, 889-1692, Japan. Electronic address: hironobu_tsubouchi@med.miyazaki-u.ac.jp.
³ Department of Neurology, Respirology, Endocrinology and Metabolism, Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan; Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki, 889-1692, Japan.
⁴ Division of Pediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
⁵ Department of Sports and Fitness, Faculty of Wellness, Shigakkan University, 55 Nakoyama, Yokone, Obu, 474-8651, Japan.
⁶ Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki, 889-1692, Japan.
⁷ Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, 920-8640, Japan.
⁸ Department of Neurology, Respirology, Endocrinology and Metabolism, Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan; Division of Inter-Organ Communication Research Project, Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.

PMID: 34929449
DOI: 10.1016/j.bbrc.2021.12.044

Abstract

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.

Keywords: ARDS; Ghrelin; Inflammation; Innate immunity; Macrophage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Respiration
Cytokines / genetics
Cytokines / metabolism
Down-Regulation*
Inflammation Mediators / metabolism
Lipopolysaccharides
Lung Injury / complications
Lung Injury / pathology*
Macrophages, Peritoneal / pathology*
Mice
Mice, Inbred C57BL
Mitochondria / metabolism
NF-kappa B / metabolism
Pneumonia / complications
Pneumonia / pathology
Pulmonary Alveoli / pathology
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Ghrelin / deficiency*
Receptors, Ghrelin / metabolism

Substances

Cytokines
Inflammation Mediators
Lipopolysaccharides
NF-kappa B
RNA, Messenger
Receptors, Ghrelin