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