| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
In this study, we analyzed the function of GADD34 in inflammatory responses against bacterial infections. We found that GADD34-deficiency enhanced tissue destruction, cell death and pro-inflammatory cytokine expression in LPS-induced acute liver injury. GADD34 inhibited hepatic apoptosis through down-regulating the eIF2α-ATF4-CHOP pathway. Then GADD34 inhibited TLR4 signaling through dephosphorylation of IKKβ, and attenuated pro-inflammatory cytokine production in macrophages. Further, we analyzed the function of GADD34 in colitis associated cancer. We found that GADD34 promoted tumor formation induced by AOM/DSS. DSS induced the expression of GADD34. GADD34 upregulated the production of IL-6 induced by DSS in colon tissue and the proliferation of epithelial cells by activation of the IL-6 /STAT3 pathway. These results indicated that GADD34 promoted AOM/DSS-induced carcinogenesis by enhancing IL-6 production from myeloid cells and subsequent STAT3 activation in epithelial cells.
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