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Interleukin 17 (IL-17) induces collagenase-3 production in human osteoarthritic chondrocytes via AP-1 dependent activation: differential activation of AP-1 members by IL-17 and IL-1beta.
J Rheumatol. 2002 Jun; 29(6):1262-72.JR

Abstract

OBJECTIVE

In osteoarthritic (OA) synovial fluid, many proinflammatory cytokines coexist and stimulate chondrocytes. As interleukin 17 (IL-17) is a catabolic cytokine, we explored its effects on collagenase-3 production. In a comparative manner we identified IL-17 and IL-1beta induced transcription factors mediating upregulation of this enzyme's production.

METHODS

Collagenase-3 levels were determined by ELISA. Transfection experiments of human OA chondrocytes were performed, with the plasmids -1599CAT and -133CAT consisting of 1.6 kb and the first proximal 133 bp containing polyomavirus enhancer A-3 (PEA-3), activating protein-1 (AP-1), and TATA box of the human collagenase-3 promoter, respectively. Electrophoretic mobility shift assays were done with the AP-1 and PEA-3 oligonucleotides derived from the human collagenase-3 promoter sequence. Supershift assays were carried out with the specific antibodies against the Jun and Fos proteins.

RESULTS

IL-17 induced collagenase-3 expression and synthesis, with an EC50 at 10 ng/ml. Transfection experiments with wild-type -1599CAT and -133CAT and their mutated AP-1 or PEA-3 derivatives revealed that the AP-1 site was essential for basal and proinflammatory cytokine induced collagenase-3 promoter activity, whereas the PEA-3 motif exerted a cooperative effect. Of note, in OA chondrocytes, IL-17 and IL-1beta induced collagenase-3 production through AP-1 occurred with differential protein complexes: IL-17 stimulation resulted in FosB activation, while IL-1beta stimulated c-Fos. Data showed a strong activation of JunB only in cells showing a higher collagenase-3 basal level and low cytokine (IL-17 and IL-1beta) inducibility, suggesting this transcription factor protein acts as a negative regulator.

CONCLUSION

We demonstrated that IL-17 and IL-1beta induced collagenase-3 production in OA chondrocytes mainly through AP-1 mediated transcriptional activity but with differential protein complexes, suggesting that some AP-1 proteins play a pivotal role in the different cytokine responses in terms of collagenase-3 production. Our data might suggest that JunB protein plays a rate-limiting step in cytokine induced collagenase-3 production in OA chondrocytes.

Authors+Show Affiliations

Osteoarthritis Research Unit, Hĵpital Notre-Dame, Centre Hospitalier de l'Université de Montréal, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

12064845

Citation

Benderdour, Mohamed, et al. "Interleukin 17 (IL-17) Induces Collagenase-3 Production in Human Osteoarthritic Chondrocytes Via AP-1 Dependent Activation: Differential Activation of AP-1 Members By IL-17 and IL-1beta." The Journal of Rheumatology, vol. 29, no. 6, 2002, pp. 1262-72.
Benderdour M, Tardif G, Pelletier JP, et al. Interleukin 17 (IL-17) induces collagenase-3 production in human osteoarthritic chondrocytes via AP-1 dependent activation: differential activation of AP-1 members by IL-17 and IL-1beta. J Rheumatol. 2002;29(6):1262-72.
Benderdour, M., Tardif, G., Pelletier, J. P., Di Battista, J. A., Reboul, P., Ranger, P., & Martel-Pelletier, J. (2002). Interleukin 17 (IL-17) induces collagenase-3 production in human osteoarthritic chondrocytes via AP-1 dependent activation: differential activation of AP-1 members by IL-17 and IL-1beta. The Journal of Rheumatology, 29(6), 1262-72.
Benderdour M, et al. Interleukin 17 (IL-17) Induces Collagenase-3 Production in Human Osteoarthritic Chondrocytes Via AP-1 Dependent Activation: Differential Activation of AP-1 Members By IL-17 and IL-1beta. J Rheumatol. 2002;29(6):1262-72. PubMed PMID: 12064845.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin 17 (IL-17) induces collagenase-3 production in human osteoarthritic chondrocytes via AP-1 dependent activation: differential activation of AP-1 members by IL-17 and IL-1beta. AU - Benderdour,Mohamed, AU - Tardif,Ginette, AU - Pelletier,Jean-Pierre, AU - Di Battista,John A, AU - Reboul,Pascal, AU - Ranger,Pierre, AU - Martel-Pelletier,Johanne, PY - 2002/6/18/pubmed PY - 2003/1/23/medline PY - 2002/6/18/entrez SP - 1262 EP - 72 JF - The Journal of rheumatology JO - J. Rheumatol. VL - 29 IS - 6 N2 - OBJECTIVE: In osteoarthritic (OA) synovial fluid, many proinflammatory cytokines coexist and stimulate chondrocytes. As interleukin 17 (IL-17) is a catabolic cytokine, we explored its effects on collagenase-3 production. In a comparative manner we identified IL-17 and IL-1beta induced transcription factors mediating upregulation of this enzyme's production. METHODS: Collagenase-3 levels were determined by ELISA. Transfection experiments of human OA chondrocytes were performed, with the plasmids -1599CAT and -133CAT consisting of 1.6 kb and the first proximal 133 bp containing polyomavirus enhancer A-3 (PEA-3), activating protein-1 (AP-1), and TATA box of the human collagenase-3 promoter, respectively. Electrophoretic mobility shift assays were done with the AP-1 and PEA-3 oligonucleotides derived from the human collagenase-3 promoter sequence. Supershift assays were carried out with the specific antibodies against the Jun and Fos proteins. RESULTS: IL-17 induced collagenase-3 expression and synthesis, with an EC50 at 10 ng/ml. Transfection experiments with wild-type -1599CAT and -133CAT and their mutated AP-1 or PEA-3 derivatives revealed that the AP-1 site was essential for basal and proinflammatory cytokine induced collagenase-3 promoter activity, whereas the PEA-3 motif exerted a cooperative effect. Of note, in OA chondrocytes, IL-17 and IL-1beta induced collagenase-3 production through AP-1 occurred with differential protein complexes: IL-17 stimulation resulted in FosB activation, while IL-1beta stimulated c-Fos. Data showed a strong activation of JunB only in cells showing a higher collagenase-3 basal level and low cytokine (IL-17 and IL-1beta) inducibility, suggesting this transcription factor protein acts as a negative regulator. CONCLUSION: We demonstrated that IL-17 and IL-1beta induced collagenase-3 production in OA chondrocytes mainly through AP-1 mediated transcriptional activity but with differential protein complexes, suggesting that some AP-1 proteins play a pivotal role in the different cytokine responses in terms of collagenase-3 production. Our data might suggest that JunB protein plays a rate-limiting step in cytokine induced collagenase-3 production in OA chondrocytes. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/12064845/Interleukin_17__IL_17__induces_collagenase_3_production_in_human_osteoarthritic_chondrocytes_via_AP_1_dependent_activation:_differential_activation_of_AP_1_members_by_IL_17_and_IL_1beta_ L2 - http://www.jrheum.org/cgi/pmidlookup?view=long&pmid=12064845 DB - PRIME DP - Unbound Medicine ER -