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Role of mitogen-activated protein kinases and tyrosine kinases on IL-1-Induced NF-kappaB activation and iNOS expression in bovine articular chondrocytes.
Nitric Oxide. 2002 Feb; 6(1):35-44.NO

Abstract

Nitric oxide (NO), produced by the inducible isoform of the NO synthase (iNOS), plays an important role in the pathophysiology of arthritic diseases. This work aimed at elucidating the role of the mitogen-activated protein kinases (MAPK), p38MAPK and p42/44MAPK, and of protein tyrosine kinases (PTK) on interleukin-1beta (IL-1)-induced iNOS expression in bovine articular chondrocytes. The specific inhibitor of the p38MAPK, SB 203580, effectively inhibited IL-1-induced iNOS mRNA and protein synthesis, as well as NO production, while the specific inhibitor of the p42/44MAPK, PD 98059, had no effect. These responses to IL-1 were also inhibited by treatment of the cells with the tyrosine kinase inhibitors, genistein and tyrphostin B42, which also prevented IL-1-induced NF-kappaB activation. The p38MAPK inhibitor, SB 203580, had no effect on IL-1-induced NF-kappaB activation. Finally, the p42/44MAPK inhibitor, PD 98059, prevented IL-1-induced AP-1 activation in a concentration that did not inhibit iNOS expression. In conclusion, this study shows that (1) PTK are part of the signaling pathway that leads to IL-1-induced NF-kappaB activation and iNOS expression; (2) the p38MAPK cascade is required for IL-1-induced iNOS expression; (3) the p42/44MAPK and AP-1 are not involved in IL-1-induced iNOS expression; and (4) NF-kappaB and the p38MAPK lie on two distinct pathways that seem to be independently required for IL-1-induced iNOS expression. Hence, inhibition of any of these two signaling cascades is sufficient to prevent iNOS expression and the subsequent production of NO in articular chondrocytes.

Authors+Show Affiliations

Faculty of Pharmacy, University of Coimbra, 3000 Coimbra, Portugal.No 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

11829533

Citation

Mendes, A Ferreira, et al. "Role of Mitogen-activated Protein Kinases and Tyrosine Kinases On IL-1-Induced NF-kappaB Activation and iNOS Expression in Bovine Articular Chondrocytes." Nitric Oxide : Biology and Chemistry, vol. 6, no. 1, 2002, pp. 35-44.
Mendes AF, Caramona MM, Carvalho AP, et al. Role of mitogen-activated protein kinases and tyrosine kinases on IL-1-Induced NF-kappaB activation and iNOS expression in bovine articular chondrocytes. Nitric Oxide. 2002;6(1):35-44.
Mendes, A. F., Caramona, M. M., Carvalho, A. P., & Lopes, M. C. (2002). Role of mitogen-activated protein kinases and tyrosine kinases on IL-1-Induced NF-kappaB activation and iNOS expression in bovine articular chondrocytes. Nitric Oxide : Biology and Chemistry, 6(1), 35-44.
Mendes AF, et al. Role of Mitogen-activated Protein Kinases and Tyrosine Kinases On IL-1-Induced NF-kappaB Activation and iNOS Expression in Bovine Articular Chondrocytes. Nitric Oxide. 2002;6(1):35-44. PubMed PMID: 11829533.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of mitogen-activated protein kinases and tyrosine kinases on IL-1-Induced NF-kappaB activation and iNOS expression in bovine articular chondrocytes. AU - Mendes,A Ferreira, AU - Caramona,M Margarida, AU - Carvalho,A Pato, AU - Lopes,M Celeste, PY - 2002/2/7/pubmed PY - 2003/4/4/medline PY - 2002/2/7/entrez SP - 35 EP - 44 JF - Nitric oxide : biology and chemistry JO - Nitric Oxide VL - 6 IS - 1 N2 - Nitric oxide (NO), produced by the inducible isoform of the NO synthase (iNOS), plays an important role in the pathophysiology of arthritic diseases. This work aimed at elucidating the role of the mitogen-activated protein kinases (MAPK), p38MAPK and p42/44MAPK, and of protein tyrosine kinases (PTK) on interleukin-1beta (IL-1)-induced iNOS expression in bovine articular chondrocytes. The specific inhibitor of the p38MAPK, SB 203580, effectively inhibited IL-1-induced iNOS mRNA and protein synthesis, as well as NO production, while the specific inhibitor of the p42/44MAPK, PD 98059, had no effect. These responses to IL-1 were also inhibited by treatment of the cells with the tyrosine kinase inhibitors, genistein and tyrphostin B42, which also prevented IL-1-induced NF-kappaB activation. The p38MAPK inhibitor, SB 203580, had no effect on IL-1-induced NF-kappaB activation. Finally, the p42/44MAPK inhibitor, PD 98059, prevented IL-1-induced AP-1 activation in a concentration that did not inhibit iNOS expression. In conclusion, this study shows that (1) PTK are part of the signaling pathway that leads to IL-1-induced NF-kappaB activation and iNOS expression; (2) the p38MAPK cascade is required for IL-1-induced iNOS expression; (3) the p42/44MAPK and AP-1 are not involved in IL-1-induced iNOS expression; and (4) NF-kappaB and the p38MAPK lie on two distinct pathways that seem to be independently required for IL-1-induced iNOS expression. Hence, inhibition of any of these two signaling cascades is sufficient to prevent iNOS expression and the subsequent production of NO in articular chondrocytes. SN - 1089-8603 UR - https://www.unboundmedicine.com/medline/citation/11829533/Role_of_mitogen_activated_protein_kinases_and_tyrosine_kinases_on_IL_1_Induced_NF_kappaB_activation_and_iNOS_expression_in_bovine_articular_chondrocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1089860301903787 DB - PRIME DP - Unbound Medicine ER -