0.5 Gy gamma radiation suppresses production of TNF-alpha through up-regulation of MKP-1 in mouse macrophage RAW264.7 cells.

Low- or intermediate-dose gamma radiation appears to have the capacity to ameliorate certain types of diseases, including allergic conditions, when examined under specific exposure conditions and with specific animal models, though the molecular mechanisms involved remain to be fully clarified. We investigated the anti-inflammatory effects of intermediate-dose gamma radiation by examining its effects on the activation state of p38 MAPK and the production of cytokines in mouse macrophage RAW264.7 cells. Dephosphorylation of both ERK1/2 and p38 MAPK was observed at 15 min after irradiation (0.5-1 Gy from a (137)Cs source) concomitant with a significant increase in the expression of MKP-1, which dephosphorylates ERK1/2 and p38 MAPK. Since activated p38 MAPK mediates TNF-alpha production, we examined the effect of radiation on LPS-induced activation of p38 MAPK and TNF-alpha production. The activation of p38 MAPK and production of TNF-alpha induced by LPS treatment were both suppressed in preirradiated cells. LPS-induced production of TNF-alpha was enhanced by knockdown of MKP-1. These results indicate that 0.5 Gy gamma radiation would cause up-regulation of MKP-1, leading to inactivation of p38 MAPK and suppression of TNF-alpha production, in cells of mouse macrophages cell line.