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

Title
Inhibition of insulin-like growth factor receptor-1 reduces necroptosis-related markers and attenuates LPS-induced lung injury in mice
Authors
Lee S.H.Shin J.H.Song J.H.Leem A.Y.Park M.S.Kim Y.S.Chang J.Chung K.S.
Ewha Authors
이수환
Issue Date
2018
Journal Title
Biochemical and Biophysical Research Communications
ISSN
0006-291XJCR Link
Citation
Biochemical and Biophysical Research Communications vol. 498, no. 4, pp. 877 - 883
Keywords
AdultIGF-1 receptorLipopolysaccharideLung injuryNecroptosisRespiratory distress syndrome
Publisher
Elsevier B.V.
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
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)-1β, IL-6, IL-10, tumour necrosis factor-α, 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. © 2018 Elsevier Inc.
DOI
10.1016/j.bbrc.2018.03.074
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의료원 > 의료원 > Journal papers
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