PMID- 30556841
OWN - NLM
STAT- MEDLINE
DCOM- 20191206
LR  - 20191217
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 22
IP  - 23
DP  - 2018 Dec
TI  - NLRP12 promotes host resistance against Pseudomonas aeruginosa keratitis 
      inflammatory responses through the negative regulation of NF-kappaB signaling.
PG  - 8063-8075
LID - 16496 [pii]
LID - 10.26355/eurrev_201812_16496 [doi]
AB  - OBJECTIVE: To investigate the role of NLRP12 in regulating Pseudomonas aeruginosa 
      (P. aeruginosa) keratitis. MATERIALS AND METHODS: Real-Time-PCR and Western blot 
      were performed to measure the NLRP12 level in corneas and bone marrow-derived 
      macrophages (BMDMs) of C57BL/6 (B6) mice. B6 mice received a subconjunctival 
      injection of lentivirus expressing active NLRP12 (NLRP12-lentivirus) or 
      Ctl-lentivirus (as control), followed by infection of P. aeruginosa. The clinical 
      score, slit lamp and bacterial plate count of mice were evaluated. In addition, 
      myeloperoxidase (MPO) was detected to assess the infiltration of 
      polymorphonuclear neutrophil (PMN). Cytokine levels were measured by Real 
      Time-PCR and ELISA. Meanwhile, the bacterial burden was also evaluated. The 
      activation of NF-kappaB signaling was determined by pIkappaBalpha/IkappaBalpha levels based on 
      Western blot and NF-kappaB-dependent Luciferase activity on the basis of Luciferase 
      assays using 293T cells. RESULTS: NLRP12 mRNA and protein levels were decreased 
      in B6 corneas and BMDMs after P. aeruginosa infection. The over-expression of 
      NLRP12 in B6 corneas significantly ameliorated the severity of corneal disease, 
      bacterial burden, PMN infiltration and pro-inflammatory cytokine expression. In 
      vitro analysis demonstrated that the up-regulation of NLRP12 suppressed 
      pro-inflammatory cytokine production and enhanced bacterial clearance in RAW264.7 
      cells. The protein levels of pIkappaBalpha and IkappaBalpha were signi fi cantly decreased after 
      NLRP12-lentivirus treatment compared with that of Ctl-lentivirus. NF-kappaB-dependent 
      Luciferase activity was potently inhibited by NLRP12 infected with P. aeruginosa 
      or cotransfected with the downstream signaling molecules including IKKalpha and IKKbeta 
      in 293T cells. CONCLUSIONS: NLRP12 decreases the severity of P. aeruginosa 
      keratitis, reduces corneal inflammation and bacterial burden through the 
      down-regulation of the NF-kappaB signaling pathway.
FAU - Deng, Q-C
AU  - Deng QC
AD  - Department of Laboratory, Longhua District Central Hospital, Longhua District, 
      Shenzhen, China. u8atg097ywq@sina.com.
FAU - Deng, C-T
AU  - Deng CT
FAU - Li, W-S
AU  - Li WS
FAU - Shu, S-W
AU  - Shu SW
FAU - Zhou, M-R
AU  - Zhou MR
FAU - Kuang, W-B
AU  - Kuang WB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Cytokines)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NLRP12 protein, mouse)
SB  - IM
MH  - Animals
MH  - Bacterial Load
MH  - Cornea/*metabolism/microbiology
MH  - Cytokines/genetics/metabolism
MH  - Disease Models, Animal
MH  - Eye Infections, Bacterial/genetics/*metabolism/microbiology/prevention & control
MH  - Female
MH  - HEK293 Cells
MH  - Host-Pathogen Interactions
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Keratitis/genetics/*metabolism/microbiology/prevention & control
MH  - Macrophages/metabolism/microbiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microbial Viability
MH  - NF-kappa B/*metabolism
MH  - Neutrophil Infiltration
MH  - Neutrophils/metabolism/microbiology
MH  - Pseudomonas Infections/genetics/*metabolism/microbiology/prevention & control
MH  - Pseudomonas aeruginosa/*pathogenicity
MH  - RAW 264.7 Cells
MH  - Signal Transduction
EDAT- 2018/12/18 06:00
MHDA- 2019/12/18 06:00
CRDT- 2018/12/18 06:00
PHST- 2018/12/18 06:00 [entrez]
PHST- 2018/12/18 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
AID - 16496 [pii]
AID - 10.26355/eurrev_201812_16496 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8063-8075. doi: 
      10.26355/eurrev_201812_16496.