Necroptosis Mediates Cigarette Smoke-Induced Inflammatory Responses in Macrophages.
Int J Chron Obstruct Pulmon Dis
; 15: 1093-1101, 2020.
Article
en En
| MEDLINE
| ID: mdl-32546997
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 andMethods:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Humo
/
Necroptosis
/
Macrófagos
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Chron Obstruct Pulmon Dis
Año:
2020
Tipo del documento:
Article