PMID- 32546997
OWN - NLM
STAT- MEDLINE
DCOM- 20210625
LR  - 20220531
IS  - 1178-2005 (Electronic)
IS  - 1176-9106 (Print)
IS  - 1176-9106 (Linking)
VI  - 15
DP  - 2020
TI  - Necroptosis Mediates Cigarette Smoke-Induced Inflammatory Responses in 
      Macrophages.
PG  - 1093-1101
LID - 10.2147/COPD.S233506 [doi]
AB  - 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-kappaB 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.
CI  - (c) 2020 Wang et al.
FAU - Wang, Yong
AU  - Wang Y
AD  - Department of Respiratory and Critical Care Medicine, First Affiliated Hospital 
      of Anhui Medical University, Hefei 230022, People's Republic of China.
FAU - Wang, Xiao-Ke
AU  - Wang XK
AD  - Department of Respiratory and Critical Care Medicine, First Affiliated Hospital 
      of Anhui Medical University, Hefei 230022, People's Republic of China.
FAU - Wu, Pei-Pei
AU  - Wu PP
AD  - Department of Respiratory and Critical Care Medicine, First Affiliated Hospital 
      of Anhui Medical University, Hefei 230022, People's Republic of China.
FAU - Wang, Yi
AU  - Wang Y
AD  - Department of Respiratory and Critical Care Medicine, First Affiliated Hospital 
      of Anhui Medical University, Hefei 230022, People's Republic of China.
FAU - Ren, Liang-Yu
AU  - Ren LY
AD  - Department of Respiratory and Critical Care Medicine, First Affiliated Hospital 
      of Anhui Medical University, Hefei 230022, People's Republic of China.
FAU - Xu, Ai-Hui
AU  - Xu AH
AD  - Department of Respiratory and Critical Care Medicine, First Affiliated Hospital 
      of Anhui Medical University, Hefei 230022, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20200518
PL  - New Zealand
TA  - Int J Chron Obstruct Pulmon Dis
JT  - International journal of chronic obstructive pulmonary disease
JID - 101273481
RN  - 0 (Smoke)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Macrophages/*drug effects
MH  - Mice
MH  - *Necroptosis
MH  - Pulmonary Disease, Chronic Obstructive/etiology
MH  - *Smoke/adverse effects
PMC - PMC7244448
OTO - NOTNLM
OT  - NF-kappaB pathway
OT  - cigarette smoke
OT  - inflammatory response
OT  - macrophage
OT  - necroptosis
COIS- The authors report no conflicts of interest in this work.
EDAT- 2020/06/18 06:00
MHDA- 2021/06/29 06:00
PMCR- 2020/05/18
CRDT- 2020/06/18 06:00
PHST- 2019/10/08 00:00 [received]
PHST- 2020/03/12 00:00 [accepted]
PHST- 2020/06/18 06:00 [entrez]
PHST- 2020/06/18 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2020/05/18 00:00 [pmc-release]
AID - 233506 [pii]
AID - 10.2147/COPD.S233506 [doi]
PST - epublish
SO  - Int J Chron Obstruct Pulmon Dis. 2020 May 18;15:1093-1101. doi: 
      10.2147/COPD.S233506. eCollection 2020.