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Mediation of interleukin-1beta-induced transforming growth factor beta1 expression by activator protein 4 transcription factor in primary cultures of bovine articular chondrocytes: possible cooperation with activator protein 1.
Arthritis Rheum. 2003 Jun; 48(6):1569-81.AR

Abstract

OBJECTIVE

Interleukin-1 (IL-1) and transforming growth factor beta1 (TGFbeta1) play major roles in osteoarticular diseases, exerting opposite effects on both the catabolism and anabolism of cartilage matrix. Previous findings suggest that IL-1 and TGFbeta1 could function in a feedback interaction. However, the effect exerted by IL-1 on expression of TGFbeta by articular chondrocytes is, so far, poorly understood. The present study was carried out to determine the influence of IL-1beta on the expression of TGFbeta1 by bovine articular chondrocytes (BACs) in primary culture.

METHODS

BAC primary cultures were treated with IL-1beta, and TGFbeta1 messenger RNA (mRNA) steady-state levels and protein expression were measured by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Transient transfection of TGFbeta1 gene promoter constructs was performed to delineate the DNA sequences that mediate the IL-1beta effect. Electrophoretic mobility shift assays (EMSAs) and supershift analysis were used to characterize the transcription factors binding to these sequences.

RESULTS

Cultured BACs responded to IL-1beta exposure by exhibiting an increase of TGFbeta1 expression at both the mRNA and protein levels. The effect was found to be mediated by a major 80-bp sequence located between -732 and -652 upstream of the transcription initiation site. EMSA and supershift analysis revealed that the transcription factors activator protein 4 (AP-4) and AP-1 specifically bound to the -720/-696 part of this sequence under IL-1beta treatment. Overexpression of AP-4 in the BAC cultures resulted in stimulation of the transcriptional activity of the -732/+11 TGFbeta1 promoter construct through the same IL-1beta-responsive element.

CONCLUSION

IL-1beta induces an increase of TGFbeta1 in articular chondrocytes through activation of AP-4 and AP-1 binding to the TGFbeta1 gene promoter. These findings may help us understand the role of IL-1beta in the disease process. Notwithstanding its deleterious effect on cartilage, IL-1 could initiate the repair response displayed by injured cartilage in the early stages of osteoarthritis through its ability to enhance TGFbeta1 expression by local chondrocytes.

Authors+Show Affiliations

Laboratory of Connective Tissue Biochemistry, Caen, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12794825

Citation

Andriamanalijaona, R, et al. "Mediation of Interleukin-1beta-induced Transforming Growth Factor Beta1 Expression By Activator Protein 4 Transcription Factor in Primary Cultures of Bovine Articular Chondrocytes: Possible Cooperation With Activator Protein 1." Arthritis and Rheumatism, vol. 48, no. 6, 2003, pp. 1569-81.
Andriamanalijaona R, Felisaz N, Kim SJ, et al. Mediation of interleukin-1beta-induced transforming growth factor beta1 expression by activator protein 4 transcription factor in primary cultures of bovine articular chondrocytes: possible cooperation with activator protein 1. Arthritis Rheum. 2003;48(6):1569-81.
Andriamanalijaona, R., Felisaz, N., Kim, S. J., King-Jones, K., Lehmann, M., Pujol, J. P., & Boumediene, K. (2003). Mediation of interleukin-1beta-induced transforming growth factor beta1 expression by activator protein 4 transcription factor in primary cultures of bovine articular chondrocytes: possible cooperation with activator protein 1. Arthritis and Rheumatism, 48(6), 1569-81.
Andriamanalijaona R, et al. Mediation of Interleukin-1beta-induced Transforming Growth Factor Beta1 Expression By Activator Protein 4 Transcription Factor in Primary Cultures of Bovine Articular Chondrocytes: Possible Cooperation With Activator Protein 1. Arthritis Rheum. 2003;48(6):1569-81. PubMed PMID: 12794825.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mediation of interleukin-1beta-induced transforming growth factor beta1 expression by activator protein 4 transcription factor in primary cultures of bovine articular chondrocytes: possible cooperation with activator protein 1. AU - Andriamanalijaona,R, AU - Felisaz,N, AU - Kim,S-J, AU - King-Jones,K, AU - Lehmann,M, AU - Pujol,J-P, AU - Boumediene,K, PY - 2003/6/10/pubmed PY - 2003/7/4/medline PY - 2003/6/10/entrez SP - 1569 EP - 81 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 48 IS - 6 N2 - OBJECTIVE: Interleukin-1 (IL-1) and transforming growth factor beta1 (TGFbeta1) play major roles in osteoarticular diseases, exerting opposite effects on both the catabolism and anabolism of cartilage matrix. Previous findings suggest that IL-1 and TGFbeta1 could function in a feedback interaction. However, the effect exerted by IL-1 on expression of TGFbeta by articular chondrocytes is, so far, poorly understood. The present study was carried out to determine the influence of IL-1beta on the expression of TGFbeta1 by bovine articular chondrocytes (BACs) in primary culture. METHODS: BAC primary cultures were treated with IL-1beta, and TGFbeta1 messenger RNA (mRNA) steady-state levels and protein expression were measured by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Transient transfection of TGFbeta1 gene promoter constructs was performed to delineate the DNA sequences that mediate the IL-1beta effect. Electrophoretic mobility shift assays (EMSAs) and supershift analysis were used to characterize the transcription factors binding to these sequences. RESULTS: Cultured BACs responded to IL-1beta exposure by exhibiting an increase of TGFbeta1 expression at both the mRNA and protein levels. The effect was found to be mediated by a major 80-bp sequence located between -732 and -652 upstream of the transcription initiation site. EMSA and supershift analysis revealed that the transcription factors activator protein 4 (AP-4) and AP-1 specifically bound to the -720/-696 part of this sequence under IL-1beta treatment. Overexpression of AP-4 in the BAC cultures resulted in stimulation of the transcriptional activity of the -732/+11 TGFbeta1 promoter construct through the same IL-1beta-responsive element. CONCLUSION: IL-1beta induces an increase of TGFbeta1 in articular chondrocytes through activation of AP-4 and AP-1 binding to the TGFbeta1 gene promoter. These findings may help us understand the role of IL-1beta in the disease process. Notwithstanding its deleterious effect on cartilage, IL-1 could initiate the repair response displayed by injured cartilage in the early stages of osteoarthritis through its ability to enhance TGFbeta1 expression by local chondrocytes. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/12794825/Mediation_of_interleukin_1beta_induced_transforming_growth_factor_beta1_expression_by_activator_protein_4_transcription_factor_in_primary_cultures_of_bovine_articular_chondrocytes:_possible_cooperation_with_activator_protein_1_ L2 - https://doi.org/10.1002/art.11020 DB - PRIME DP - Unbound Medicine ER -