微膠細胞在中樞神經系統（CNS）的免疫反應發揮了關鍵作用。類似其他神經退行性疾病，微膠細胞堆積在腦膠質瘤觀察。但是，微膠細胞在腦膠質瘤中的促進作用和抗腫瘤反應，是值得商確的。它已知在全身性的發炎反應時，促發炎細胞激素，包括白細胞介素1-(IL-1) 和腫瘤壞死因子(TNF-)等會大量的增加。這些細胞激素不僅可以調控周圍組織局部發炎反應，同時也引發中樞神經系統的神經發炎。多重效能腫瘤壞死因子，可藉由腫瘤壞死因子受體I型(TNFR1)的和II型(TNFR2)所觸發複雜的訊息傳遞。我們實驗室最近的研究結果顯示，腹腔內(i.p.)注射脂多醣(LPS)至TNFR2-/- 小鼠(0.5 mg/kg/day)顯著增加了大腦皮層中CD11b+微膠細胞/巨噬細胞。此外，在TNFR2-/-小鼠大腦將C6膠質瘤細胞植入之後與野生型(WT)、TNFR2+/-小鼠相比有明顯的腫瘤形成。同時，TNFR2-/-小鼠植入C6膠質瘤細胞後再接受周邊注射LPS的小鼠有較低的存活率。 而在C6膠質瘤細胞植入前接受周邊注射LPS TNFR2-/-與WT、TNFR2+/-小鼠相比，存活率則沒有顯著差異。然而，在C6膠質瘤細胞植入TNFR2-/-小鼠前先給予LPS腹腔注射，觀察到腫瘤體積的增加。我們的結果顯示TNFR2表現缺失誘發腦部微膠細胞活化和促進腦膠質瘤的形成有正向關係。 
關鍵字：腫瘤壞死因子第二型受體、脂多醣、膠質瘤 

Microglia play a critical role in the immune response of central nervous system (CNS). Similar to other neurodegenerative disorders, microglia are accumulated in gliomas. However, the role of microglia in glioma progress and anti-tumor activity is arguable. It has been known that systemic inflammation increases the production of pro-inflammatory cytokines, including interleukin-1 (IL-1) and tumor necrosis factor- (TNF-). These cytokines not only mediate local inflammation in peripheral tissues, but also trigger neuroinflammation in the CNS. The multiple actions of TNF- are derived from the complexity of TNF receptor type I (TNFRI) and type II (TNFRII)-triggered signaling pathways. Our recent findings have showed that intraperitoneal (ip) injection with lipopolysaccharide (LPS) into TNFRII-/- mice (0.5 mg/kg/day) significantly increased CD11b+ microglia/macrophages in the cortex. In addition, progressive C6-glioma cell formed tumor was observed at the implanted site of TNFRII-/- mice brain when compared to that seen in TNFRII+/- mice. We also observed the lower survival rate of TNFRII-/- mice receiving peripheral LPS injection after C6 glioma cells when compared to that detected in wild type (WT) and TNFRII+/- mice. Yet, No different change in the survival rate of TNFRII-/- mice treated with peripheral LPS injection before C6 glioma cell implantation when compared to that observed in WT and TNFRII+/- mice. However, increased tumor volume was observed in TNFRII-/- mice receiving LPS prior to C6 glioma implantation. Together, the results suggest that TNFRII deficiency and microglia activation are positively correlated with enhancement of glioma formation.
Key words：TNF receptor type II、lipopolysaccharide、glioma

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