Chronic obstructive pulmonary disease (
COPD), primarily attributed to cigarette
smoke (CS), is characterized by multiple pathophysiological changes, including oxidative stress and
inflammation.
Stromal interaction molecule 1 (STIM1) is a Ca2+ sensor that regulates Ca2+ entry in different types of cells. The present study aimed to explore the relationship between CS-induced oxidative stress and
inflammation, as well as the functional role of STIM1 thereinto. Our results showed that the
reactive oxygen species (ROS)/STIM1/Ca2+ axis played a critical role in CS-induced secretion of
interleukin (IL)-8 in human alveolar macrophages. Specifically, smokers with
COPD (SC) showed higher levels of ROS in the lung tissues compared with healthy non-smokers (HN). STIM1 was upregulated in the lung tissues of
COPD patients. The expression of STIM1 was positively associated with ROS levels and negatively correlated with pulmonary function. The expression of STIM1 was also increased in the bronchoalveolar lavage fluid (BALF) macrophages of
COPD patients and PMA-differentiated THP-1 macrophages stimulated by cigarette
smoke extract (CSE). Additionally, CSE-induced upregulation of STIM1 in PMA-differentiated THP-1 macrophages was inhibited by pretreatment with
N-acetylcysteine (NAC), a ROS scavenger. Transfection with
small interfering RNA (
siRNA) targeting STIM1 and pretreatment with NAC alleviated CSE-induced increase in intracellular Ca2+ levels and
IL-8 expression. Furthermore, pretreatment with
SKF-96365 and 2-APB, the inhibitors of Ca2+ influx, suppressed CSE-induced secretion of
IL-8. In conclusion, our study demonstrates that CSE-induced ROS production may increase the expression of STIM1 in macrophages, which further promotes the release of
IL-8 by regulating Ca2+ entry. These data suggest that STIM1 may play a crucial role in CSE-induced ROS production and
inflammation, and participate in the pathogenesis of
COPD.