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Title: Prophylactic proopiomelanocortin expression alleviates capsaicin-induced neurogenic inflammation in rat trachea. Author: Liu GS, Huang HT, Lin CJ, Shi JY, Liu LF, Tseng RT, Weng WT, Lam HC, Wen ZH, Cheng TL, Hsu KS, Tai MH. Journal: Shock; 2009 Dec; 32(6):645-50. PubMed ID: 19333140. Abstract: Neurogenic inflammation frequently causes acute plasma leakage in airways and life-threatening pulmonary edema. However, limited strategies are available to alleviate neurogenic inflammation. Proopiomelanocortin (POMC) is the precursor of anti-inflammatory melanocortins, which have been proposed of therapeutic potential for various inflammatory diseases. The present study aimed to evaluate whether peripheral POMC expression ameliorated capsaicin-induced acute neurogenic inflammation in rat trachea. Prophylactic POMC expression was achieved by intravenous injection of adenovirus encoding POMC (Ad-POMC), which led to POMC expression in livers and elevated plasma adrenocorticotropin levels for approximately 60 days. After gene delivery for 7 days, neurogenic inflammation was induced in rats by capsaicin injection. The extent of capsaicin-evoked plasma leakage in trachea was alleviated in Ad-POMC-treated rats compared with animals of control groups (P < 0.01). Moreover, the number of endothelial gaps in tracheal venules was also significantly decreased in Ad-POMC-treated animals (P < 0.01). Prophylactic POMC expression, however, did not alter the basal substance P (SP) expression or the capsaicin-induced SP elevation in trachea and circulation. Instead, cell cultures studies revealed that POMC overexpression or application of POMC-derived melanocortins potently inhibited the SP-induced migration of endothelial cells (P < 0.01), thereby possibly contributing to the attenuation of endothelial gap formation and plasma leakage. The present study indicates that the anti-inflammatory POMC gene vector or melanocortins may constitute a therapeutic alternative for neurogenic inflammation.[Abstract] [Full Text] [Related] [New Search]