Skip to main content

Production of interleukin (IL)-1 receptor antagonist by human articular chondrocytes

IL-1 receptor antagonist (IL-1Ra) is a member of the IL-1 family, which acts as a natural IL-1 inhibitor. The balance between IL-1 and IL-1Ra plays an important role in the course of various inflammatory diseases, such as arthritis. IL-1Ra is produced as different isoforms, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, 2, 3), derived from the same gene. We examined the production of IL-1Ra isoforms by cultured human articular chondrocytes in response to various cytokines. The concentrations of IL-1Ra were measured by ELISA in conditioned media and cell lysates. The levels of IL-1Ra were undetectable in culture supernatants of untreated cells, but were significantly increased by IL-1β (IL-1). IL-1Ra secretion was first detectable after 24 hours and increased progressively thereafter, for at least 72 hours. In contrast, the cell lysates contained very low levels of IL-1Ra, even in response to IL-1 stimulation, suggesting that articular chondrocytes produce essentially the sIL-1Ra isoform. IL-6, which had no effect on its own, enhanced the effect of IL-1, while dexamethasone (dex) prevented the response. By RT-PCR, we observed that IL-1 and IL-6 induced mainly the production of sIL-1Ra mRNA. Furthermore, IL-1 alone or combined with IL-6 increased the levels of nascent unspliced sIL-1Ra mRNA, suggesting that sIL-1Ra expression is regulated at the transcriptional level. Consistently, reporter gene assays performed in immortalized human chondrocytes, C20/A4, showed increased sIL-1Ra promoter activity in response to IL-1 and IL-6. In conclusion, human articular chondrocytes produce sIL-1Ra in response to IL-1. This effect, which is enhanced by IL-6 and inhibited by dex, reflects increased transcription from the sIL-1Ra promoter. The production of sIL-1Ra by chondrocytes may have a protective effect against articular inflammatory and catabolic responses.

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Palmer, G., Guerne, P., Mezin, F. et al. Production of interleukin (IL)-1 receptor antagonist by human articular chondrocytes. Arthritis Res Ther 4, 63 (2002). https://doi.org/10.1186/ar507

Download citation

Keywords

  • Receptor Antagonist
  • Dexamethasone
  • Reporter Gene
  • Conditioned Medium
  • Promoter Activity