title: Controlled Release of Interleukin-1 Receptor Antagonist from Hyaluronic Acid-Chitosan Microspheres Attenuates Interleukin-1β-Induced Inflammation and Apoptosis in Chondrocytes.
abstract: This paper investigates the protective effect of interleukin-1 receptor antagonist (IL-1Ra) released from hyaluronic acid chitosan (HA-CS) microspheres in a controlled manner on IL-1β-induced inflammation and apoptosis in chondrocytes. The IL-1Ra release kinetics was characterized by an initial burst release, which was reduced to a linear release over eight days. Chondrocytes were stimulated with 10 ng/ml IL-1βand subsequently incubated with HA-CS-IL-1Ra microspheres. The cell viability was decreased by IL-1β, which was attenuated by HA-CS-IL-1Ra microspheres as indicated by an MTT assay. ELISA showed that HA-CS-IL-1Ra microspheres inhibited IL-1β-induced inflammation by attenuating increases in NO2-and prostaglandin E2 levels as well as increase in glycosaminoglycan release. A terminal deoxyribonucleotide transferase deoxyuridine triphosphate nick-end labeling assay revealed that the IL-1β-induced chondrocyte apoptosis was decreased by HA-CS-IL-1Ra microspheres. Moreover, HA-CS-IL-1Ra microspheres blocked IL-1β-induced chondrocyte apoptosis by increasing B-cell lymphoma 2 (Bcl-2) and decreasing Bcl-2-associated X protein and caspase-3 expressions at mRNA and protein levels, as indicated by reverse-transcription quantitative polymerase chain reaction and western blot analysis, respectively. The results of the present study indicated that HA-CS-IL-1Ra microspheres as a controlled release system of IL-1Ra possess potential anti-inflammatory and antiapoptotic properties in rat chondrocytes due to their ability to regulate inflammatory factors and apoptosis associated genes.
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, No. 238, Liberation Road, Hubei, Wuhan 430060, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qiu
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, No. 238, Liberation Road, Hubei, Wuhan 430060, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gong
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, No. 238, Liberation Road, Hubei, Wuhan 430060, China.
authors.forename: Qi-Ting
authors.initials: QT
authors.lastname: He
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, No. 238, Liberation Road, Hubei, Wuhan 430060, China.
authors.forename: Pang-Hu
authors.identifier: 0000-0002-7020-4258
authors.initials: PH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D020011:Protective Agents / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D006025:Glycosaminoglycans; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D006820:Hyaluronic Acid; D048271:Chitosan; D053148:Caspase 3; D015232:Dinoprostone