PRophylactic proopiomelanocortin expression alleviates capsaicin-induced neurogenic inflammation in rat trachea

Guei Sheung Liu, Hung Tu Huang, Che Jen Lin, Jhih Yin Shi, Li Feng Liu, Rue Tseng Tseng, Wen Tsan Weng, Hing Chung Lam, Zhi Hong Wen, Tian Lu Cheng, Kuei Sen Hsu, Ming Hong Tai

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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.

Original languageEnglish
Pages (from-to)645-650
Number of pages6
JournalShock
Volume32
Issue number6
DOIs
Publication statusPublished - 2009 Dec 1

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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    Liu, G. S., Huang, H. T., Lin, C. J., Shi, J. Y., Liu, L. F., Tseng, R. T., Weng, W. T., Lam, H. C., Wen, Z. H., Cheng, T. L., Hsu, K. S., & Tai, M. H. (2009). PRophylactic proopiomelanocortin expression alleviates capsaicin-induced neurogenic inflammation in rat trachea. Shock, 32(6), 645-650. https://doi.org/10.1097/SHK.0b013e3181a5aa10