Production of interleukin-1 receptor antagonist by human articular chondrocytes
Interleukin-1 receptor antagonist (IL-1Ra) is a natural IL-1 inhibitor possessing anti-inflammatory properties. IL-1Ra is produced as different isoforms, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, icIL-1Ra2 and icIL-1Ra3), derived from the same gene. We examined the production of IL-1Ra species by cultured human articular chondrocytes in response to various cytokines. The levels of IL-1Ra were undetectable in culture supernatants of untreated cells, but were significantly increased by IL-1β. Cell lysates contained very low levels of IL-1Ra, even in response to IL-1β, suggesting that chondrocytes produce predominantly sIL-1Ra. IL-6, which had no effect on its own, enhanced the effect of IL-1β, while dexamethasone prevented the response. We observed by RT-PCR that IL-1β and IL-6 induced primarily the production of sIL-1Ra mRNA. Furthermore, IL-1β 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. Reporter gene assays in immortalized chondrocytes, C-20/A4, consistently showed increased sIL-1Ra promoter activity in response to IL-1β and IL-6. In conclusion, human articular chondrocytes produce sIL-1Ra in response to IL-1β and IL-6. The production of sIL-1Ra by chondrocytes may have a protective effect against articular inflammatory and catabolic responses.
Complete Metadata
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| description | Interleukin-1 receptor antagonist (IL-1Ra) is a natural IL-1 inhibitor possessing anti-inflammatory properties. IL-1Ra is produced as different isoforms, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, icIL-1Ra2 and icIL-1Ra3), derived from the same gene. We examined the production of IL-1Ra species by cultured human articular chondrocytes in response to various cytokines. The levels of IL-1Ra were undetectable in culture supernatants of untreated cells, but were significantly increased by IL-1β. Cell lysates contained very low levels of IL-1Ra, even in response to IL-1β, suggesting that chondrocytes produce predominantly sIL-1Ra. IL-6, which had no effect on its own, enhanced the effect of IL-1β, while dexamethasone prevented the response. We observed by RT-PCR that IL-1β and IL-6 induced primarily the production of sIL-1Ra mRNA. Furthermore, IL-1β 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. Reporter gene assays in immortalized chondrocytes, C-20/A4, consistently showed increased sIL-1Ra promoter activity in response to IL-1β and IL-6. In conclusion, human articular chondrocytes produce sIL-1Ra in response to IL-1β and IL-6. The production of sIL-1Ra by chondrocytes may have a protective effect against articular inflammatory and catabolic responses. |
| distribution |
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| identifier | https://healthdata.gov/api/views/g45v-qsw4 |
| issued | 2025-07-14 |
| keyword |
[
"articular-chondrocytes",
"cytokine-response",
"il-1ra",
"nih",
"osteoarthritis-research"
]
|
| landingPage | https://healthdata.gov/d/g45v-qsw4 |
| modified | 2025-09-06 |
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| theme |
[
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|
| title | Production of interleukin-1 receptor antagonist by human articular chondrocytes |
