MyJournals Home  

RSS FeedsThe complement receptor C5aR2 promotes protein kinase R expression and contributes to NLRP3 inflammasome activation and HMGB1 release from macrophages [Signal Transduction] (Journal of Biological Chemistry)

 
 

24 may 2019 13:02:52

 
The complement receptor C5aR2 promotes protein kinase R expression and contributes to NLRP3 inflammasome activation and HMGB1 release from macrophages [Signal Transduction] (Journal of Biological Chemistry)
 


The NLR family pyrin domain-containing 3 (NLRP3) inflammasome is a multimeric protein complex that mediates maturation of the cytokines IL-1? and IL-18 as well as release of the proinflammatory protein high-mobility group box 1 (HMGB1) and contributes to several inflammatory diseases, including sepsis, gout, and type 2 diabetes. In this context, the well-studied active complement fragment C5a and its receptor C5aR1 or C5aR2 orchestrate the inflammatory responses in many diseases. Although a C5a-C5aR interaction in NLRP3-associated diseases has been suggested, little is known about the details of C5a-C5aR cross-talk with the NLRP3 inflammasome in macrophages. In this study, using mice and murine macrophages and cytokines, immunoblotting, siRNA, and quantitative real-time PCR assays, we demonstrate that C5aR2 deficiency restricts activation of the NLRP3 inflammasome and release of HMGB1 both in vitro and in vivo. Mechanistically, we found that C5aR2 promotes NLRP3 activation by amplifying dsRNA-dependent PKR expression, which is an important NLRP3-activating factor. We also observed that elevation of PKR expression because of the C5a-C5aR2 interaction depends on the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase pathway and type I IFN signaling. In conclusion, these findings reveal that C5aR2 contributes to NLRP3 inflammasome activation and HMGB1 release from macrophages.


 
82 viewsCategory: Biochemistry
 
A basic protein, N25, from a mollusk modifies calcium carbonate morphology and shell biomineralization [Methods and Resources] (Journal of Biological Chemistry)
Common motifs in ETAA1 and TOPBP1 required for ATR kinase activation [DNA and Chromosomes] (Journal of Biological Chemistry)
 
 
blog comments powered by Disqus


MyJournals.org
The latest issues of all your favorite science journals on one page

Username:
Password:

Register | Retrieve

Search:

Biochemistry


Copyright © 2008 - 2024 Indigonet Services B.V.. Contact: Tim Hulsen. Read here our privacy notice.
Other websites of Indigonet Services B.V.: Nieuws Vacatures News Tweets Nachrichten