Necroptosis Mediates Cigarette Smoke-Induced Inflammatory Responses in Macrophages.

Abstract

Introduction:

Cigarette smoke (CS)-induced inflammation in macrophages is involved in the pathological process of chronic obstructive pulmonary disease (COPD). Necroptosis, which is a form of programmed necrosis, has a close relationship with robust inflammation, while its roles in COPD are unclear.

Materials and Methods:

Necroptosis markers were measured in mouse alveolar macrophages and cultured bone marrow-derived macrophages (BMDMs). Necroptosis inhibitors were used to block necroptosis in BMDMs, and inflammatory cytokines were detected. We further explored the related signaling pathways.

Results:

In this study, we demonstrated the way in which necroptosis, in addition to its upstream and downstream signals, regulates CS-induced inflammatory responses in macrophages. We observed that CS exposure caused a significant increase in the levels of necroptosis markers (receptor interacting kinases [RIPK] 1 and 3) in mouse alveolar macrophages and BMDMs. Pharmacological inhibition of RIPK1 or 3 caused a significant suppression in CS extract (CSE)-induced inflammatory cytokines, chemokine ligands (CXCL) 1 and 2, and interleukin (IL)-6 in BMDMs. CSE-induced necroptosis was regulated by mitochondrial reactive oxygen species (mitoROS), which also promoted inflammation in BMDMs. Furthermore, necroptosis regulated CSE-induced inflammatory responses in BMDMs, most likely through activation of the nuclear factor-κB pathway.

Conclusion:

Taken together, our results demonstrate that mitoROS-dependent necroptosis is essential for CS-induced inflammation in BMDMs and suggest that inhibition of necroptosis in macrophages may represent effective therapeutic approaches for COPD patients.

• Authors: Yong Wang, Xiao-Ke Wang, Pei-Pei Wu, Yi Wang, Liang-Yu Ren, Ai-Hui Xu
• Journal: International journal of chronic obstructive pulmonary disease (Int J Chron Obstruct Pulmon Dis) Vol. 15 Pg. 1093-1101 ( 2020) ISSN: 1178-2005 [Electronic] New Zealand
• PMID: 32546997 (Publication Type: Journal Article)
• Copyright: © 2020 Wang et al.

Chemical References

• Smoke

Topics

• Animals
• Cells, Cultured
• Macrophages (drug effects)
• Mice
• Necroptosis
• Pulmonary Disease, Chronic Obstructive (etiology)
• Smoke (adverse effects)