Piperlongumine attenuates collagen-induced arthritis via expansion of myeloid-derived suppressor cells and inhibition of the activation of fibroblast-like synoviocytes.

Abstract

Piperlonguminine (PL), a key compound from the Piper longum fruit, is known to exhibit anti‑tumor and anti‑inflammatory activities. However, little is known about its effects on collagen‑induced arthritis (CIA). Fibroblast‑like synoviocytes (FLS) have a pivotal role in the development of rheumatoid arthritis (RA). Myeloid‑derived suppressor cells (MDSCs) are able to suppress T cell responses and have important roles in the regulation of autoimmune arthritis. The current study investigated whether PL alters the progression of RA. It was determined that PL reduces the arthritis score and histopathologic lesions in a mouse model of CIA. PL also reduces the expression levels of serum anti‑collagen II antibodies (anti‑CⅡ), tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑1β, IL‑23 and IL‑17 in CIA mice. In draining lymph nodes (DLNs), MDSCs were significantly expanded, however, the number of Th17 cells was markedly decreased by PL treatment. Additionally, PL reduced secretion of IL‑1β, IL‑23 and IL‑17 by TNF‑α‑stimulated human RA FLS. PL significantly inhibited the migration and invasion of TNF‑α‑stimulated human RA FLS. These results indicate that PL may be a candidate therapeutic agent for the treatment of RA, via the expansion of MDSCs and the inhibition of the Th17 response and activation of FLS.