Complement component 3 protects human bronchial epithelial cells from cigarette smoke-induced oxidative stress and prevents incessant apoptosis

Abstract

The complement component 3 (C3) is a pivotal element of the complement system and plays an important role in innate immunity. A previous study showed that intracellular C3 was upregulated in airway epithelial cells (AECs) from individuals with end-stage chronic obstructive pulmonary disease (COPD). Accumulating evidence has shown that cigarette smoke extract (CSE) induces oxidative stress and apoptosis in AECs. Therefore, we investigated whether C3 modulated cigarette smoke-induced oxidative stress and apoptosis in AECs and participated in the pathogenesis of COPD. We found increased C3 expression, together with increased oxidative stress and apoptosis, in a cigarette smoke-induced mouse model of COPD and in AECs from patients with COPD. Different concentrations of CSEinduced C3 expression in 16HBE cells in vitro. Interestingly, C3 knockdown (KD) exacerbated oxidative stress and apoptosis in 16HBE cells exposed to CSE. Furthermore, C3 exerted its pro-survival effects through JNK inhibition, while exogenous C3 partially rescued CSE-induced cell death and oxidative stress in C3 KD cells. These data indicate that locally produced C3 is an important pro-survival molecule in AECs under cigarette smoke exposure, revealing a potentially novel mechanism in the pathogenesis of COPD.

Hypoxia-induced Complement Component 3 Promotes Aggressive Tumor Growth in the Glioblastoma Microenvironment

“…In this study, we show that cells of the GBM microenvironment upregulate the central protein of the complement system, C3, under hypoxic conditions. Presence of C3 during cellular stress, such as hypoxia or irradiation, led to increased survival of glioma cells, supporting previous findings that C3 can act as a pro-survival factor during cellular stress [46,48,49].…”

Blood and urine multi-omics analysis of the impact of e-vaping, smoking, and cessation: from exposome to molecular responses

“…Upregulated complement proteins in smokers included complement factor I (CFI P05156), complement factor B (CFB P00751), complement factor H (CFH P08603), complement component C4 (C4A P0C0L4), and complement component C9 (C9 P02748). To our knowledge, the literature has not clearly highlighted elevated complement protein levels for smokers 23 . This observation suggests that smoking may have an impact on the complement system, which is a crucial immune system component.…”

“…Beyond the markers (potentially) associated with smoke exposure, the untargeted metabolomics data also reflected the use of common drugs, such as ibuprofen and acetaminophen. While not leveraged in the current study, such information on the exposome for common pharmaceutical drugs can support data interpretation, for example, when effects on the immune system are investigated 23,24 . The application of this approach is, for example, illustrated by a recent publication by Suhre et al 25 .…”

Complement C3 reduces apoptosis in human cardiomyocytes

“…The copyright holder for this preprint (which this version posted May 2, 2023. ; https://doi.org/10.1101/2023.05.01.538962 doi: bioRxiv preprint seems to protect airway epithelial cells in a cigarette smoking model (Pei et al, 2022), and airway epithelial cells readily take up C3 from exogenous sources to mitigate apoptosis (Kulkarni et al, 2019). C3 was also reported to inhibit apoptosis in bullous-like skin inflammation (Zheng et al, 2020).…”