title: Prophylactic proopiomelanocortin expression alleviates capsaicin-induced neurogenic inflammation in rat trachea.
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.
authors.affiliation: Department of Medical Education & Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Guei-Sheung
authors.initials: GS
authors.lastname: Liu
authors.forename: Hung-Tu
authors.initials: HT
authors.lastname: Huang
authors.forename: Che-Jen
authors.initials: CJ
authors.lastname: Lin
authors.forename: Jhih-Yin
authors.initials: JY
authors.lastname: Shi
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Liu
authors.forename: Rue-Tseng
authors.initials: RT
authors.lastname: Tseng
authors.forename: Wen-Tsan
authors.initials: WT
authors.lastname: Weng
authors.forename: Hing-Chung
authors.initials: HC
authors.lastname: Lam
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
authors.forename: Tian-Lu
authors.initials: TL
authors.lastname: Cheng
authors.forename: Kuei-Sen
authors.initials: KS
authors.lastname: Hsu
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tai