The NLRP3 inflammasome is a central regulator of inflammation in many common diseases, including atherosclerosis and type 2 diabetes, driving the production of pro-inflammatory mediators such as IL-1β and IL-18. Due to its function as an inflammatory gatekeeper, expression and activation of NLRP3 need to be tightly regulated. In this study, we highlight novel post-transcriptional mechanisms that can modulate NLRP3 expression. We have identified the RNA-binding protein Tristetraprolin (TTP) as a negative regulator of NLRP3 in human macrophages. TTP targets AU-rich elements in the NLRP3 3′-untranslated region (UTR) and represses NLRP3 expression. Knocking down TTP in primary macrophages leads to an increased induction of NLRP3 by LPS, which is also accompanied by increased Caspase-1 and IL-1β cleavage upon NLRP3, but not AIM2 or NLRC4 inflammasome activation. Furthermore, we found that human NLRP3 can be alternatively polyadenylated, producing a short 3′-UTR isoform that excludes regulatory elements, including the TTP- and miRNA-223-binding sites. Because TTP also represses IL-1β expression, it is a dual inhibitor of the IL-1β system, regulating expression of the cytokine and the upstream controller NLRP3.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2qlPLYz
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 18 January 2017 Source: Free Radical Biology and Medicine Author(s): Jayne Louise Wilson, Frédéric Boui...
-
Publication date: March 2017 Source: Free Radical Biology and Medicine, Volume 104 from #AlexandrosSfakianakis via Alexandros G.Sfak...
-
Publication date: July 2017 Source: European Journal of Cancer, Volume 79 Author(s): Simon Pernot, Cecile Badoual, Magali Terme, Florence...
-
Inflammation is an important component of diabetic retinal damage. We previously reported that a novel β-adrenergic receptor agonist, Compou...
-
An ambitious plan to save a melting glacier in the Swiss Alps with showers of artificial snow will be tested this summer from #AlexandrosS...
-
by Yiquan Wu, Adrian Prager, Simone Boos, Moritz Resch, Ilija Brizic, Michael Mach, Sabrina Wildner, Laura Scrivano, Barbara Adler Herpesv...
-
Background: Hidradenitis suppurativa (HS) is a long-term skin disorder associated with high levels of psychological distress and significan...
-
A mass-change-based method based on output-only data for the rescaling of mode shapes in operational modal analysis (OMA) is introduced. The...
-
Summary Ultrasound guidance is becoming standard practice for needle-based interventions in anaesthetic practice, such as vascular access ...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου