SQSTM1-dependent autophagic degradation of PKM2 inhibits the production of mature IL1B/IL-1 β and contributes to LIPUS-mediated anti-inflammatory effect.

SQSTM1-dependent autophagic degradation of PKM2 inhibits the production of mature IL1B/IL-1β and contributes to LIPUS-mediated anti-inflammatory effect.
Autophagy. 2019 Sep 10;:
Authors: Zhang B, Chen H, Ouyang J, Xie Y, Chen L, Tan Q, Du X, Su N, Ni Z, Chen L
Abstract
Synovitis is implicated in the pathology of osteoarthritis (OA) and significantly contributes to the development of OA. As a noninvasive physical therapy, low-intensity pulsed ultrasound (LIPUS) has been reported to possess anti-inflammatory effect in recent years. However, the role of LIPUS on synovitis of OA and the underlying mechanisms are little known. The present study showed that LIPUS ameliorated synovial inflammation in destabilization of the medial meniscus (DMM) mouse model and air pouch model, and alleviated pain gait patterns of DMM mouse. LIPUS dramatically inhibited the production of mature IL1B/IL-1β (interleukin 1 beta) in vitro and in vivo. In addition, LIPUS upregulated the macroautophagy/autophagy level as well as accelerated the formation of an SQSTM1 (sequestosome1)-PKM (pyruvate kinase, muscle) complex in the lipopolysaccharide (LPS)-adenosine triphosphate (ATP)-treated macrophages. Besides, LIPUS downregulated the level of PKM2 in LPS-ATP-treated macrophages, which could be reversed by SQSTM1 knockdown. In brief, the present study for the first time demonstrates that LIPUS inhibits the production of mature IL1B partially via SQSTM1-dependent a...

Source: Autophagy - September 9, 2019 Category: Cytology Authors: Zhang B, Chen H, Ouyang J, Xie Y, Chen L, Tan Q, Du X, Su N, Ni Z, Chen L Tags: Autophagy Source Type: research