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Interleukin 17, a nitric oxide-producing cytokine with a peroxynitrite-independent inhibitory effect on proteoglycan synthesis.
J Rheumatol. 2002 Dec; 29(12):2602-10.JR

Abstract

OBJECTIVE

To compare the potency of 2 cytokines, interleukin 17 (IL-17) and IL-1beta, on rat cartilage proteoglycan synthesis with special attention to nitric oxide (NO) and peroxynitrite formation.

METHODS

Chondrocytes in alginate beads were stimulated with human recombinant (rh) IL-17 (0.03 to 300.0 ng/ml) and/or rhIL-1beta (0.25 to 25.0 ng/ml) in the presence or not of L-NMMA or CuDips. Alternatively, rats were injected with either IL-17 (10.0 micro g) or IL-1beta (1.0 micro g) into each knee joint. NO concentrations were determined by a spectrofluorimetric assay, proteoglycan synthesis by 35SO4-2 incorporation, peroxynitrite generation by immunostaining for 3-nitrotyrosine, and IL-1beta mRNA expression by reverse transcription-polymerase chain reaction.

RESULTS

IL-17 inhibited proteoglycan synthesis and increased NO production, both in vitro and in vivo, without inducing expression of IL-1beta mRNA in cartilage. Additive effects were observed when IL-17 was combined with low concentrations of IL-1. Surprisingly, a similar NO synthesis between IL-1 and IL-17 led to a less suppressive effect of IL-17 on cartilage anabolism than with IL-1. Both in vitro and in vivo, peroxynitrite formation was extensive with IL-1beta, but negligible or nonexistent with IL-17. L-NMMA and CuDips completely corrected the suppressive effect of IL-1beta on proteoglycan synthesis, unlike with IL-17.

CONCLUSION

These data showed that NO is weakly involved in the IL-17 mediated inhibition of proteoglycan synthesis in rat. NO overload may not be predictive of any inhibitory effect on cartilage anabolism, but instead superoxide is a key regulator of NO contribution to chondrocyte dysfunction. Since IL-17 is a NO-producing cytokine with additive effects when combined with IL-1, it may play a pivotal role in cartilage destruction during rheumatoid arthritis, for which infiltrating cells produce high levels of superoxide and proinflammatory cytokines.

Authors+Show Affiliations

Faculté de Médecine, Vandoeuvre-lès-Nancy, France.No affiliation info availableNo affiliation info availableNo 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12465160

Citation

Pacquelet, Sandrine, et al. "Interleukin 17, a Nitric Oxide-producing Cytokine With a Peroxynitrite-independent Inhibitory Effect On Proteoglycan Synthesis." The Journal of Rheumatology, vol. 29, no. 12, 2002, pp. 2602-10.
Pacquelet S, Presle N, Boileau C, et al. Interleukin 17, a nitric oxide-producing cytokine with a peroxynitrite-independent inhibitory effect on proteoglycan synthesis. J Rheumatol. 2002;29(12):2602-10.
Pacquelet, S., Presle, N., Boileau, C., Dumond, H., Netter, P., Martel-Pelletier, J., Pelletier, J. P., Terlain, B., & Jouzeau, J. Y. (2002). Interleukin 17, a nitric oxide-producing cytokine with a peroxynitrite-independent inhibitory effect on proteoglycan synthesis. The Journal of Rheumatology, 29(12), 2602-10.
Pacquelet S, et al. Interleukin 17, a Nitric Oxide-producing Cytokine With a Peroxynitrite-independent Inhibitory Effect On Proteoglycan Synthesis. J Rheumatol. 2002;29(12):2602-10. PubMed PMID: 12465160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin 17, a nitric oxide-producing cytokine with a peroxynitrite-independent inhibitory effect on proteoglycan synthesis. AU - Pacquelet,Sandrine, AU - Presle,Nathalie, AU - Boileau,Christelle, AU - Dumond,Hélène, AU - Netter,Patrick, AU - Martel-Pelletier,Johanne, AU - Pelletier,Jean-Pierre, AU - Terlain,Bernard, AU - Jouzeau,Jean-Yves, PY - 2002/12/5/pubmed PY - 2003/5/8/medline PY - 2002/12/5/entrez SP - 2602 EP - 10 JF - The Journal of rheumatology JO - J. Rheumatol. VL - 29 IS - 12 N2 - OBJECTIVE: To compare the potency of 2 cytokines, interleukin 17 (IL-17) and IL-1beta, on rat cartilage proteoglycan synthesis with special attention to nitric oxide (NO) and peroxynitrite formation. METHODS: Chondrocytes in alginate beads were stimulated with human recombinant (rh) IL-17 (0.03 to 300.0 ng/ml) and/or rhIL-1beta (0.25 to 25.0 ng/ml) in the presence or not of L-NMMA or CuDips. Alternatively, rats were injected with either IL-17 (10.0 micro g) or IL-1beta (1.0 micro g) into each knee joint. NO concentrations were determined by a spectrofluorimetric assay, proteoglycan synthesis by 35SO4-2 incorporation, peroxynitrite generation by immunostaining for 3-nitrotyrosine, and IL-1beta mRNA expression by reverse transcription-polymerase chain reaction. RESULTS: IL-17 inhibited proteoglycan synthesis and increased NO production, both in vitro and in vivo, without inducing expression of IL-1beta mRNA in cartilage. Additive effects were observed when IL-17 was combined with low concentrations of IL-1. Surprisingly, a similar NO synthesis between IL-1 and IL-17 led to a less suppressive effect of IL-17 on cartilage anabolism than with IL-1. Both in vitro and in vivo, peroxynitrite formation was extensive with IL-1beta, but negligible or nonexistent with IL-17. L-NMMA and CuDips completely corrected the suppressive effect of IL-1beta on proteoglycan synthesis, unlike with IL-17. CONCLUSION: These data showed that NO is weakly involved in the IL-17 mediated inhibition of proteoglycan synthesis in rat. NO overload may not be predictive of any inhibitory effect on cartilage anabolism, but instead superoxide is a key regulator of NO contribution to chondrocyte dysfunction. Since IL-17 is a NO-producing cytokine with additive effects when combined with IL-1, it may play a pivotal role in cartilage destruction during rheumatoid arthritis, for which infiltrating cells produce high levels of superoxide and proinflammatory cytokines. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/12465160/Interleukin_17_a_nitric_oxide_producing_cytokine_with_a_peroxynitrite_independent_inhibitory_effect_on_proteoglycan_synthesis_ L2 - http://www.jrheum.org/cgi/pmidlookup?view=long&pmid=12465160 DB - PRIME DP - Unbound Medicine ER -