Is increased sensitivity to apoptosis induced by methotrexate mediated by JNK?
Our results support a model whereby MTX inhibits reduction of dihydrobiopterin to tetrahydrobiopterin, resulting in increased production of ROS, increased JNK activity, and increased sensitivity to apoptosis. The finding of increased jun levels in patients with RA receiving low-dose MTX supports the notion that this pathway is activated by MTX in vivo and may contribute to the efficacy of MTX in inflammatory disease.
These results suggest that PAP-I mRNA might be modulated by endotoxemia, independent of cerulein-pancreatitis. There were no strong correlations between PAP-I mRNA expression and the severity of pancreatitis.