PMID- 32146317 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240227 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 82 DP - 2020 Mar 5 TI - Theobromine mitigates IL-1beta-induced oxidative stress, inflammatory response, and degradation of type II collagen in human chondrocytes. PG - 106226 LID - S1567-5769(19)32197-6 [pii] LID - 10.1016/j.intimp.2020.106226 [doi] AB - Osteoarthritis is one of the major causes of disability in elderly adults. Chondrocytes are responsible for the formation and remodeling of articular cartilage in joint tissue. The dysfunction of chondrocytes is a significant factor in the development of osteoarthritis. In the current study, we found that theobromine, a constituent of the cacao plant, possesses a preventive effect against interleukin (IL)-1beta-induced chondrocyte dysfunction. Theobromine ameliorates IL-1beta-induced production of cellular reactive oxygen species (ROS) and inflammatory mediators including cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)). The presence of theobromine suppresses IL-1beta-induced inducible nitro oxide synthase (iNOS) expression and cellular nitro oxide (NO) production. Theobromine also suppresses IL-1beta-induced production of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1), as well as matrix metalloproteinases (MMP)-3 and MMP-13. Additionally, theobromine mitigates IL-1beta-induced type II collagen degradation. Mechanistically, we show that theobromine inhibits IL-1beta-induced IkappaBalpha activation, nuclear factor-kappaB (NF-kappaB) protein p65 accumulation, and transfected NF-kappaB promoter activity, indicating that theobromine suppresses the NF-kappaB pathway in chondrocytes. Collectively, our study demonstrates that the natural molecule theobromine has a protective effect to counter cytokine-induced chondrocyte dysfunction, implying its beneficial effect in the prevention of osteoarthritis. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Gu, Ronghe AU - Gu R AD - Department of Orthopedics, The First People's Hospital of Nanning, The Fifth Affiliated Hospital of Guangxi Medical University, China. FAU - Shi, Yu AU - Shi Y AD - Department of Spinal Surgery, Affiliated Hospital of Youjiang Medical College for Nationalities, China. FAU - Huang, Weiguo AU - Huang W AD - Department of Orthopedics, The First People's Hospital of Nanning, The Fifth Affiliated Hospital of Guangxi Medical University, China. FAU - Lao, Chendeng AU - Lao C AD - Department of Orthopedics, The First People's Hospital of Nanning, The Fifth Affiliated Hospital of Guangxi Medical University, China. FAU - Zou, Zhuan AU - Zou Z AD - Department of Orthopedics, The First People's Hospital of Nanning, The Fifth Affiliated Hospital of Guangxi Medical University, China. FAU - Pan, Songmu AU - Pan S AD - Department of Orthopedics, The First People's Hospital of Nanning, The Fifth Affiliated Hospital of Guangxi Medical University, China. FAU - Huang, Zonggui AU - Huang Z AD - Department of Orthopedics, The First People's Hospital of Nanning, The Fifth Affiliated Hospital of Guangxi Medical University, China. Electronic address: jeremy5052@163.com. LA - eng PT - Journal Article DEP - 20200305 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 SB - IM OTO - NOTNLM OT - Chondrocyte dysfunction OT - IL-1beta OT - NF-kappaB OT - Theobromine COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/03/09 06:00 MHDA- 2020/03/09 06:01 CRDT- 2020/03/09 06:00 PHST- 2019/09/28 00:00 [received] PHST- 2020/01/16 00:00 [revised] PHST- 2020/01/16 00:00 [accepted] PHST- 2020/03/09 06:01 [medline] PHST- 2020/03/09 06:00 [pubmed] PHST- 2020/03/09 06:00 [entrez] AID - S1567-5769(19)32197-6 [pii] AID - 10.1016/j.intimp.2020.106226 [doi] PST - aheadofprint SO - Int Immunopharmacol. 2020 Mar 5;82:106226. doi: 10.1016/j.intimp.2020.106226.