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Transcriptional suppression by interleukin‐1 and interferon‐γ of type II collagen gene expression in human chondrocytes
Abstract
Type II collagen is one of the predominant extracellular matrix macromolecules in cartilage responsible for maintenance of integrity of this specialized tissue. We showed previously that interleukin‐1 (IL‐1) and interferon‐γ (IFN‐γ) are capable of decreasing the levels of α1 (II) procollagen mRNA and suppressing the synthesis of type II collagen in cultured human chondrocytes. Data reported here show that these effects of IL‐1 and IFN‐γ on the expression of the human type II collagen gene (COL2A1) are mediated primarily at the transcriptional level. This conclusion is based on three types of experimental evidence: (1) in nuclear run‐off assays, preincubation of chondrocytes with either IL‐1 or IFN‐γ decreased COL2A1 transcription; (2) experiments with the protein synthesis inhibitor cycloheximide and the transcriptional inhibitor 5,6‐dichloro‐1‐β‐D‐ribofuranosylbenzimidazole (DRB) indicated that the suppression of α1 (II) procollagen mRNA by IL‐1 could not be ascribed to decreased mRNA stability; and (3) a plasmid (pCAT‐B/4.0) containing 4.0 kb of 5′‐flanking sequences of COL2A1 (−577/+3428), encompassing the promoter, exon 1 and the putative enhancer sequence in the first intron, linked to the chloramphenicol acetyltransferase (CAT) reporter gene, was transfected in human chondrocytes. A high level of expression of pCAT‐B/4.0 was observed in human chondrocytes incubated with an insulin‐containing serum substitute that is permissive for expression of the COL2A1 gene. Expression of pCAT‐B/4.0 in these cells was inhibited by either IL‐1 or IFN‐γ. Furthermore, expression of pCAT‐B/4.0 was not detected in human dermal fibroblasts. When the putative enhancer fragment in the first intron was removed, the expression in chondrocytes was greatly reduced. These studies demonstrate that expression of COL2A1 is tissue specific and that suppression by either IL‐1 or IFN‐γ is mediated primarily at the transcriptional level.
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Metadata
- Authors
- Goldring, M. B., Fukuo, K., Birkhead, J. R., Dudek, E., & Sandell, L. J.
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 1994-01
- Volume
- 54
- Issue
- 1
- Pages
- 85-99
- ISSN
- 0730-2312 (ISSN-L)
- 1097-4644
- OpenAlex
- W2085314940
- Cited by
- 173
- References
- 0
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Transcriptional suppression by interleukin‐1 and interferon‐γ of type II collagen gene expression in human chondrocytes. https://app.cochat.ai/papers/10.1002/jcb.240540110
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- Goldring, M. B., Fukuo, K., Birkhead, J. R., Dudek, E., & Sandell, L. J. (1994). Transcriptional suppression by interleukin‐1 and interferon‐γ of type II collagen gene expression in human chondrocytes. Journal of Cellular Biochemistry. https://doi.org/10.1002/jcb.240540110
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