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(Circulation Research. 2001;88:1066.)
© 2001 American Heart Association, Inc.

Integrative Physiology

ADAR1 Is Involved in the Development of Microvascular Lung Injury

Reuven Rabinovici, Koroush Kabir, Meihong Chen, Yingjun Su, Dexin Zhang, Xiaoxing Luo, Jing-Hua Yang

From the Department of Surgery (R.R., K.K., Y.S., X.L., J.-H.Y.), Yale University School of Medicine, New Haven, Conn, and Xian Biomedical Research Institute (M.C., D.Z.), Fourth Military Medical University, Xian 710032, People’s Republic of China.

Correspondence to Drs Reuven Rabinovici and Jing-Hua Yang, Section of Trauma and Surgical Critical Care, Yale University School of Medicine, 333 Cedar Street (LH-118), New Haven, CT 06520. E-mail reuven.rabinovici@yale.edu or jinhua.yang{at}yale.edu

Abstract—Deamination of adenosine on pre-mRNA to inosine is a recently discovered process of posttranscription modification of pre-mRNA, termed A-to-I RNA editing, which results in the production of proteins not inherent in the genome. The present study aimed to identify a role for A-to-I RNA editing in the development of microvascular lung injury. To that end, the pulmonary expression and activity of the RNA editase ADAR1 were evaluated in a mouse model of endotoxin (15 mg/kg IP)–induced microvascular lung injury (n=5) as well as in cultured alveolar macrophages stimulated with endotoxin, live bacteria, or interferon. ADAR1 expression and activity were identified in sham lungs that were upregulated in lungs from endotoxin-treated mice (at 2 hours). Expression was localized to polymorphonuclear and monocytic cells. These events preceded the development of pulmonary edema and leukocyte accumulation in lung tissue and followed the local production of interferon-, a known inducer of ADAR1 in other cell systems. ADAR1 was found to be upregulated in alveolar macrophages (MH-S cells) stimulated with endotoxin (1 to 100 µg/mL), live Escherichia coli (5x10⁷ colony-forming units), or interferon- (1000 U/mL). Taken together, these data suggest that ADAR1 may play a role in the pathogenesis of microvascular lung injury possibly through induction by interferon.

Key Words: ADAR1 • adult respiratory distress syndrome • endotoxin • interferon • RNA editing

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