ADAR1 is involved in the development of microvascular lung injury

Deamination of adenosine on pre-mRNA to inosine is a recently discovered pr ocess of posttranscription modification of pre-mRNA, termed A-to-I RNA edit ing, 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 expres sion 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 bacteri a, or interferon. ADAR1 expression and activity were identified in sham lun gs that were upregulated in lungs from endotoxin-treated mice (at 2 hours), Expression was localized to polymorphonuclear and monocytic cells. These e vents preceded the development of pulmonary edema and leukocyte accumulatio n in lung tissue and followed the local production of interferon-gamma, a k nown inducer of ADAR1 in other cell systems. ADAR1 was found to be upregula ted in alveolar macrophages (MH-S cells) stimulated with endotoxin (1 to 10 0 mug/mL), live Escherichia coli (5 x 10(7) colony-forming units), or inter feron-gamma (1000 U/mL), Taken together, these data suggest that ADAR1 may play a role in the pathogenesis of microvascular lung injury possibly throu gh induction by interferon.