LATE-BREAKING ABSTRACT: miR-877 and its target protein HDAC6 are involved in airway inflammation

Abstract

Background: Several pathophysiological and molecular mechanisms including epigenetics have been shown to participate in the etiology of chronic obstructive pulmonary disease (COPD).

Aims and objectives: This study was aimed to 1) explore the role of miR-877 and 2) to determine its target proteins in airway inflammation related to COPD.

Methods: miRNA expression and their target proteins in cell lines and lung tissues from rat with airway inflammation were measured by quantitative real-time PCR, western blotting and ELISA.

Results: miR-877 was identified to be decreased in miRNA array analysis of NR8383 cells treated with LPS, which was further validated through real-time PCR. HDAC6, a predicted miR-877 target, was significantly up-regulated in NR8383 cells treated with LPS. Moreover, IL-6 and IL-8 production was increased concomitantly and such effect could be ablated by pretreatment with a HDAC6 specific inhibitor or by addition of buthioninesulfoximine (BSO), a specific inhibitor of GSH synthesis. Overexpression of miR-877 decreased HDAC6 expression and production of IL-6 and IL-8. In addition, long-term treatment of rat with cigarette smokes (CS), an airway inflammation model, also led to down-regulated miR-877 expression, which was accompanied by up-regulated HDAC6 expression and subsequent IL-8 and IL-6 secretion. Furthermore, treatment with carbocysteine (S-CMC), an anti-oxidant and mucolytic agent which produces GSH, significantly decreased miR-877 target protein HDAC6 expression as well as the secretion of IL-6 and IL-8.

Conclusions: miR-877 and its target protein HDAC6 played a key role in the airway inflammatory responses. LPS/CS-induced epigenetic changes could be modulated by S-CMC through GSH.