INDUCTION OF SYNTHESIS AND RELEASE OF INTERLEUKIN-8 FROM HUMAN ARTICULAR CHONDROCYTES AND CARTILAGE EXPLANTS

Objective. The activation of neutrophils in the joint space may contribute to the destruction of cartilage matrix observed in rheumatoid arthritis. The capacity of articular chondrocytes to synthesize and secrete interleukin-8 (IL-8) and GROalpha, two potent neutrophil chemoattractant peptides, was investigated to determine whether cartilage itself could serve as a source of these small cytokines. Methods. Induction of IL-8 and GRO protein was studied both at the messenger RNA (mRNA) and the protein level by reverse transcriptase/polymerase chain reaction and metabolic labeling, respectively. Results. Strong induction of IL-8 was observed in primary cultures of articular chondrocytes as well as in cartilage explants stimulated with IL-1beta. The increased secretion of the IL-8 protein was accompanied by corresponding increases in mRNA levels. In contrast to other connective tissue cells, a peptide corresponding in molecular size to the GRO proteins was only weakly induced in cartilage explants or primary chondrocyte cultures. However, mRNA for all 3 members of the GRO family was easily detectable in cultured chondrocytes following stimulation with IL-1beta. In explanted cartilage, mRNA for only GROgamma was found to be induced. Newly synthesized IL-8 was slowly released from cartilage explants over a prolonged time in culture. Conclusion. The results suggest that synthesis and secretion of the diverse members of the IL-8/GRO family is regulated in a tissue-specific or cell-specific manner. The slow release of IL-8 from articular cartilage following induction by IL-1beta could establish a chemotactic gradient toward the articular surface and mediate the migration and attachment of neutrophils and lymphocytes to this tissue.