Inflammasome-independent role of NLRP12 in suppressing colonic inflammation regulated by Blimp-1.
NLRP12 is a member of the Nod-like receptor (NLR). Previous studies have reported enhanced colitis-associated inflammatory responses in NLRP12-deficient mice. In this study, we sought to investigate the role of NLRP12 in DSS-stimulated proinflammatory response in dendritic cells and mice colitis, and the molecular mechanisms involved in the development of the inflammation. Our results showed that down-regulation of NLRP12 is required for DSS-induced release of proinflammatory cytokines IL-1β and TNF-α; that PR domain zinc finger protein 1 (also known as Blimp-1) induces NLRP12 down-regulation during DSS-induced proinflammatory response and colitis; and that TLR4 is implicated in the up-regulation of Blimp-1 that led to the down-regulation of NLRP12 expression in DSS-induced colitis. Taken together, the results suggest that the TLR4-Blimp-1 axis promotes DSS induced experimental colitis through the down-regulation of NLRP12.
Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Fushan
F
Shi
College of Animal Science and Technology, Zhejiang A&F University, Lin'an 311300, China.
Yang
Y
Yang
Trustchem Co., Ltd., Nanjing 210029, China.
Mohammed
M
Kouadir
Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Wei
W
Xu
Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Songhua
S
Hu
Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Tiancheng
T
Wang
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D016264:Dextran Sulfate; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074462:Positive Regulatory Domain I-Binding Factor 1 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D058847:Inflammasomes; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; C553199:NLRP12 protein, mouse; C513258:Prdm1 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D000074462:Positive Regulatory Domain I-Binding Factor 1
Blimp-1; NLRP12; TLR4; colitis; inflammation