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Inhibition of insulin-like growth factor receptor-1 reduces necroptosis-related markers and attenuates LPS-induced lung injury in mice

 Su Hwan Lee  ;  Ju Hye Shin  ;  Joo Han Song  ;  Ah Young Leem  ;  Moo Suk Park  ;  Young Sam Kim  ;  Joon Chang  ;  Kyung Soo Chung 
 Biochemical and Biophysical Research Communications, Vol.498(4) : 877-883, 2018 
Journal Title
 Biochemical and Biophysical Research Communications 
Issue Date
Animals ; CD/metabolism Antigens ; Apoptosis/drug effects ; Bronchoalveolar Lavage Fluid/chemistry/cytology/immunology ; Cadherins/metabolism ; Lipopolysaccharides ; Lung/metabolism ; Lung Injury/chemically induced/*prevention & control ; Macrophages/metabolism ; Mice ; Necrosis/*etiology ; IGF Type 1/antagonists & inhibitors/*pharmacology/physiology Receptor ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism
Adult ; IGF-1 receptor ; Lipopolysaccharide ; Lung injury ; Necroptosis ; Respiratory distress syndrome
Insulin-like growth factor-1 (IGF-1) levels are known to increase in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome. Herein, we investigated the role of IGF-1 in lipopolysaccharide (LPS)-induced lung injury. In LPS-treated cells, expressions of receptor-interacting protein 3 (RIP3) and phosphorylated mixed lineage kinase domain-like protein (MLKL) were decreased in IGF-1 receptor small interfering RNA (siRNA)-treated cells compared to control cells. The levels of pro-inflammatory cytokines including interleukin (IL)-1beta, IL-6, IL-10, tumour necrosis factor-alpha, and macrophage inflammatory protein 2/C-X-C motif chemokine ligand 2 in the supernatant were significantly reduced in IGF-1 receptor siRNA-treated cells compared to control cells. In LPS-induced murine lung injury model, total cell counts, polymorphonuclear leukocytes counts, and pro-inflammatory cytokine levels in the BALF were significantly lower and histologically detected lung injury was less common in the group treated with IGF-1 receptor monoclonal antibody compared to the non-treated group. On western blotting, RIP3 and phosphorylated MLKL expressions were relatively decreased in the IGF-1 receptor monoclonal antibody group compared to the non-treated group. IGF-1 may be associated with RIP3-mediated necroptosis in vitro, while blocking of the IGF-1 pathway may reduce LPS-induced lung injuries in vivo.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
김영삼(Kim, Young Sam)
박무석(Park, Moo Suk) ORCID logo https://orcid.org/0000-0003-0820-7615
송주한(Song, Joo Han)
임아영(Leem, Ah Young)
장준(Chang, Joon)
정경수(Jung, Kyung Soo)
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