Gene interactions and pathways from curated databases and text-mining
Nitric Oxide 2002, PMID: 11829533

Role of mitogen-activated protein kinases and tyrosine kinases on IL-1-Induced NF-kappaB activation and iNOS expression in bovine articular chondrocytes.

Mendes, A Ferreira; Caramona, M Margarida; Carvalho, A Pato; Lopes, M Celeste

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.

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Text Mining Data

NF-kappaB → IL-1: " Role of mitogen activated protein kinases and tyrosine kinases on IL-1 Induced NF-kappaB activation and iNOS expression in bovine articular chondrocytes "

iNOS → IL-1: " Role of mitogen activated protein kinases and tyrosine kinases on IL-1 Induced NF-kappaB activation and iNOS expression in bovine articular chondrocytes "

iNOS → interleukin-1beta (IL-1): " 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 "

iNOS — MAPK: " 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 "

iNOS — protein tyrosine kinases ( PTK ): " 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 "

NF-kappaB → IL-1: " 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 "

NF-kappaB ⊣ p38MAPK: " The p38MAPK inhibitor, SB 203580, had no effect on IL-1 induced NF-kappaB activation "

NF-kappaB ⊣ p38MAPK: " The p38MAPK inhibitor, SB 203580, had no effect on IL-1 induced NF-kappaB activation "

NF-kappaB → IL-1: " The p38MAPK inhibitor, SB 203580, had no effect on IL-1 induced NF-kappaB activation "

AP-1 → p42/44MAPK: " Finally, the p42/44MAPK inhibitor, PD 98059, prevented IL-1 induced AP-1 activation in a concentration that did not inhibit iNOS expression "

AP-1 → p42/44MAPK: " Finally, the p42/44MAPK inhibitor, PD 98059, prevented IL-1 induced AP-1 activation in a concentration that did not inhibit iNOS expression "

AP-1 → p42/44MAPK: " Finally, the p42/44MAPK inhibitor, PD 98059, prevented IL-1 induced AP-1 activation in a concentration that did not inhibit iNOS expression "

AP-1 → IL-1: " Finally, the p42/44MAPK inhibitor, PD 98059, prevented IL-1 induced AP-1 activation in a concentration that did not inhibit iNOS expression "

NF-kappaB → IL-1: " 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 "

iNOS → p42/44MAPK: " 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 "

iNOS → p42/44MAPK: " 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 "

iNOS → p42/44MAPK: " 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 "

iNOS → AP-1: " 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 "

iNOS → IL-1: " 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 "

Manually curated Databases

No curated data.