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Endoplasmic reticulum stress (ERS)‐induced apoptosis of airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Furthermore, autophagy is closely related to ERS under apoptosis. Here, this study aimed to investigate the role of the reciprocal interaction between autophagy and ERS in the cigarette smoke extract (CSE)‐induced apoptosis of human bronchial epithelial (HBE) cells. Cell apoptosis was detected by flow cytometry analysis. Protein expression was examined by Western blot. The mRNA expression was detected using real‐time quantitative reverse transcription PCR (qRT‐PCR). The results showed that CSE treatment induced apoptosis, autophagy, and expression of ERS‐related proteins in HBE cells. Furthermore, autophagy inhibition by 3‐MA significantly decreased protein expression of GRP78, p‐PERK, and p‐eIF2α and increased CHOP, ATF4, and caspase‐4, whereas ERS inhibition by 4‐PBA led to autophagy suppression. Moreover, the CSE‐induced autophagy was diminished by knockdown of GRP78, PERK, or eIF2α but enhanced by knockdown of ATF4 or CHOP; however, the CSE‐induced HBE apoptosis was enhanced by knockdown of GRP78, PERK, or eIF2α but was attenuated by knockdown of ATF4 or CHOP. Additionally, both sodium hydrosulfide (NaHS) and melatonin attenuated the CSE‐induced apoptosis, enhanced the CSE‐induced autophagy, increased GRP78, p‐PERK, and p‐eIF2α, and decreased CHOP, ATF4, and caspase‐4, via SIRT1/ORP150 pathway. Collectively, this study provided evidence about the role of the reciprocal interaction between autophagy and ERS in CSE‐induced apoptosis of HBE cells. © 2018 IUBMB Life, 71(1):66–80, 2019 [ABSTRACT FROM AUTHOR]

• PRKCD contributes to the development of COPD caused by harmful gases or particles. • PRKCD promotes inflammation, apoptosis, mitochondrial dysfunction and MUC5AC hypersecretion in COPD. • PRKCD is a novel potential therapeutic target for COPD. Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by progressive airflow limitation and abnormal lung function due to noxious particles and gases. Although many measures are available, COPD remains one of the leading causes of morbidity and mortality worldwide. Therefore, there is an urgent need to discover novel potential therapeutic targets for COPD. Protein kinase C delta (PRKCD) is a member of the PKC family and possesses various biological properties. Recently, PRKCD has been reported to play an important role in the pathogenesis of COPD. However, the mechanisms of PRKCD on COPD are not fully elucidated. In this review, we will discuss the roles and mechanisms of PRKCD involved in the development of COPD. We systematically summarized the studies on the research progress of PRKCD in COPD based on MEDLINE/PubMed databases. PRKCD contributes to the development of COPD by promoting inflammatory response, apoptosis, mitochondrial dysfunction and MUC5AC hypersecretion. These data provide evidence that PRKCD might be a potential therapeutic target for COPD. [ABSTRACT FROM AUTHOR]