TY - JOUR AU - Nakajima, Kazuyuki AU - Ishijima, Takashi AU - Kobayashi, Hiroshi PY - 2019/05/28 TI - Induction of tumor necrosis factor alpha (TNF) expression in microglia by the accumulation of a superoxide anion donor in rat cerebral cortex JF - Medical Research Archives; Vol 7 No 5 (2019): Vol.7 Issue 5 May 2019DO - 10.18103/mra.v7i5.1928 KW - N2 - Previously we reported that endotoxin-dependent induction of tumor necrosis factor alpha (TNFexpression in microglia was significantly suppressed by the superoxide anion scavenger N-acetyl cysteine (NAC), and that microglia induced TNF in response to a superoxide anion donor 3-(4-morpholinyl)sydnonimine (SIN-1) in vitro. Those findings strongly suggested that superoxide anion is associated with the induction of TNF in microglia. However, whether TNF is actually induced in microglia in vivo remains to be determined. In the present study, we confirmed the ability of microglia to induce TNF in vitro and examined the effects of SIN-1 on microglial induction of TNF in vivo. The accumulation of SIN-1 solution in rat cerebral cortex led to the induction of TNF on the ipsilateral, but not the contralateral side. The levels of TNF in the ipsilateral cortex peaked at 6-12 h post-accumulation. Immunohistochemical study revealed that anti-TNF antibody-positive cells in the SIN-1-injected region were mainly anti-ionized Ca 2+ binding adapter molecule-1 (Iba-1) antibody-positive, suggesting that microglia are a major cell type for inducing TNF. On the other hand, interleukin 1beta (IL-1) and IL-6 were not detected in the SIN-1-injected cortex. Together, these results indicate that microglia induced TNF in vivo in response to superoxide anion. UR - https://esmed.org/MRA/mra/article/view/1928