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LJ-529, a partial peroxisome proliferator-activated receptor gamma (PPARγ) agonist and adenosine A3 receptor agonist, ameliorates elastase-induced pulmonary emphysema in mice

Archives of Pharmacal Research 2020년 43권 5호 p.540 ~ 552
부혜진 ( Boo Hye-Jin ) - Seoul National University College of Pharmacy

박소정 ( Park So-Jung ) - Seoul National University College of Pharmacy
 ( Noh Myung-Kyung ) - Seoul National University College of Pharmacy
민혜영 ( Min Hye-Young ) - Seoul National University College of Pharmacy
정락신 ( Jeong Lak-Shin ) - Seoul National University College of Pharmacy
이호영 ( Lee Ho-Young ) - Seoul National University College of Pharmacy

Abstract


Chronic obstructive pulmonary disease (COPD) is the leading cause of human death worldwide. Currently available therapies for COPD mainly relieve symptoms and preserve lung function, suggesting the need to develop novel therapeutic or preventive regimens. Because chronic inflammation is a mechanism of emphysematous lesion formation and because adenosine A3 receptor signaling and peroxisome proliferator-activated receptor gamma (PPARγ) regulate inflammation, we investigated the effect of LJ-529, a selective adenosine A3 receptor agonist and partial PPARγ agonist, on inflammation in vitro and elastase-induced pulmonary emphysema in vivo. LJ-529 markedly ameliorated elastase-induced emphysematous lesion formation in the lungs in vivo, as indicated by the restoration of pulmonary function, suppression of airspace enlargement, and downregulation of elastase-induced matrix metalloproteinase activity and apoptotic cell death in the lungs. LJ-529 induced the expression of PPARγ target genes, the activity of PPARγ and several cytokines involved in inhibiting inflammation and inducing anti-inflammatory M2-like phenotypes. Moreover, LJ-529 did not exhibit significant cytotoxicity in normal cell lines derived from various organs in vitro and induced minimal changes in body weight in vivo, suggesting no overt toxicity of LJ-529 in vitro or in vivo. These results indicate the potential of LJ-529 as a novel therapeutic/preventive agent for emphysema with limited toxicity.

키워드

LJ-529; Emphysema; Elastase; Peroxisome proliferator-activated receptor gamma
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