title: 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.
authors.affiliation: Department of Orthopedics, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Orthopedics and Traumatology, Qidong Hospital of Traditional Chinese Medicine, Nantong, Jiangsu 421600, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Orthopedics and Traumatology, Qidong Hospital of Traditional Chinese Medicine, Nantong, Jiangsu 421600, P.R. China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Orthopedics, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, P.R. China.
authors.forename: Qinggang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, P.R. China.
authors.forename: Yuchang
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000097:blood; D004148:Dioxolanes / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D018836:Inflammation Mediators / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology*; D013583:Synovial Membrane / Q000166:cytology*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D010881:Piperidones
chemical_list: D000906:Antibodies; D024043:Collagen Type II; D016207:Cytokines; D004148:Dioxolanes; D018836:Inflammation Mediators; C498077:piperlongumine; D010881:Piperidones