PMID- 32504162
OWN - NLM
STAT- MEDLINE
DCOM- 20210715
LR  - 20210715
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 43
IP  - 5
DP  - 2020 Oct
TI  - PM2.5 Exposure Induces Inflammatory Response in Macrophages via the 
      TLR4/COX-2/NF-kappaB Pathway.
PG  - 1948-1958
LID - 10.1007/s10753-020-01269-y [doi]
AB  - Fine particulate matter with an aerodynamic diameter less than 2.5 mum (PM2.5) is 
      a serious air pollutant associated with health problems. Macrophages play an 
      important role in the process of PM2.5-induced inflammation in respiratory 
      diseases. However, the detailed mechanism remains unclear. We aimed to examine 
      the mechanism of PM2.5-induced inflammation and find possible anti-inflammatory 
      inhibitors. PM2.5 was collected in Hangzhou, China, and the composition of 
      adsorbed materials on PM2.5 was characterized. RAW 254.7 cells were then treated 
      with PM2.5. Phagocytosis was observed, and inflammatory response was triggered as 
      demonstrated by the release of high levels of monocyte chemoattractant 
      protein-1(MCP-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) and 
      increased mRNA expression of inducible nitric oxide synthase (iNOS) and TNF-alpha. 
      Treatment with classic inhibitors suppressed the released pro-inflammatory 
      factors in a dose-dependent manner. Using Immunology Inflammation Compound 
      Library, we screened 70 inhibitors and clustered them based on similarities in 
      their inhibitory effects, which we detected using cytometric bead array (CBA) 
      assay. Molecular analysis revealed that the expression of toll-like receptor 4 
      (TLR4), nuclear factor kappa-B (NF-kappaB), and cyclooxygenase-2 (COX-2) was 
      increased in PM2.5-stimulated RAW 254.7 cells. Corresponding inhibitors were 
      selected, and the CBA assay verified their anti-inflammatory effects. These 
      inhibitors reduced the expression of pro-inflammatory factors, and this reduction 
      was correlated with the downregulation of the TLR4/NF-kappaB/COX-2 signaling pathway. 
      In conclusion, PM2.5 induces an inflammatory response in macrophages via 
      activation of TLR4/NF-kappaB/COX-2 signaling, and the inhibitors of this pathway are 
      potential therapeutic candidates to treat inflammatory disorders.
FAU - Fu, Huiying
AU  - Fu H
AD  - The Second Clinical Medical College, Zhejiang Chinese Medical University, 
      Hangzhou, 310053, China.
FAU - Liu, Xia
AU  - Liu X
AD  - The Second Clinical Medical College, Zhejiang Chinese Medical University, 
      Hangzhou, 310053, China.
FAU - Li, Wei
AU  - Li W
AD  - College of Medical Technology, Zhejiang Chinese Medical University, Hangzhou, 
      310053, China.
FAU - Zu, Yuyao
AU  - Zu Y
AD  - College of Medical Technology, Zhejiang Chinese Medical University, Hangzhou, 
      310053, China.
FAU - Zhou, Fangmei
AU  - Zhou F
AD  - College of Medical Technology, Zhejiang Chinese Medical University, Hangzhou, 
      310053, China.
FAU - Shou, Qiyang
AU  - Shou Q
AD  - The Second Clinical Medical College, Zhejiang Chinese Medical University, 
      Hangzhou, 310053, China. sqy133@126.com.
FAU - Ding, Zhishan
AU  - Ding Z
AUID- ORCID: 0000-0001-5740-1479
AD  - College of Medical Technology, Zhejiang Chinese Medical University, Hangzhou, 
      310053, China. dzszjtcm@163.com.
LA  - eng
GR  - 81673672/National Natural Science Foundation of China/
GR  - 81673645/National Natural Science Foundation of China/
GR  - 81873047/National Natural Science Foundation of China/
GR  - 81573677/National Natural Science Foundation of China/
GR  - LQ17H030006/Natural Science Foundation of Zhejiang Province/
PT  - Journal Article
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Particulate Matter)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Animals
MH  - Cyclooxygenase 2/*metabolism
MH  - Inflammation Mediators/*metabolism
MH  - Macrophages/drug effects/*metabolism
MH  - Mice
MH  - NF-kappa B/*metabolism
MH  - Particulate Matter/*toxicity
MH  - RAW 264.7 Cells
MH  - Signal Transduction/drug effects/physiology
MH  - Toll-Like Receptor 4/*metabolism
OTO - NOTNLM
OT  - COX-2
OT  - NF-kappaB
OT  - PM2.5
OT  - TLR4
OT  - inflammation
OT  - macrophages
EDAT- 2020/06/07 06:00
MHDA- 2021/07/16 06:00
CRDT- 2020/06/07 06:00
PHST- 2020/06/07 06:00 [pubmed]
PHST- 2021/07/16 06:00 [medline]
PHST- 2020/06/07 06:00 [entrez]
AID - 10.1007/s10753-020-01269-y [pii]
AID - 10.1007/s10753-020-01269-y [doi]
PST - ppublish
SO  - Inflammation. 2020 Oct;43(5):1948-1958. doi: 10.1007/s10753-020-01269-y.