死亡接受器誘發細胞凋亡過程中，c-FLIP扮演抑制細胞凋亡的角色。在一些慢性發炎疾病的病灶處，有巨噬細胞浸潤的現象，且這些巨噬細胞有大量c-FLIP的表現，造成巨噬細胞抗拒細胞凋亡訊息，而加強發炎現象。本研究以老鼠巨噬細胞，Raw 264.7，作為材料，探討c-FLIPL對巨噬細胞活化之影響。結果發現以LPS刺激穩定表現c-FLIPL蛋白質的Raw 264.7細胞(Raw 264.7/c-FLIPL)，會明顯增加促發炎反應細胞激素TNFα mRNA的表現及TNFα分泌，進一步分析發現造成TNFα增加的原因，是穩定表現c-FLIPL會使MyD88表現增加，進而增加p38的磷酸化，最終造成了TNFα分泌量增多，顯示c-FLIPL參與巨噬細胞引起的發炎反應。本研究證實c-FLIPL過度表現會促進發炎反應，因此在開發治療及預防發炎疾病的藥物或保健食品可以考慮將c-FLIPL做為藥物的標靶因子。

Cellular FLICE-inhibitory protein (c-FLIP) is a well-established inhibitor of death receptor-initiated apoptosis. Chronic inflammatory disease is characterized by macrophages infiltrate in the lesion location. The expression of c-FLIP in infiltrate macrophages and its correlation to accumulation of inflammatory cells in lesion tissue suggests that c-FLIP potentially extends the lifespan of macrophages and thus contributes to the progression of inflammation. In this study we attempt to verify the c-FLIPL effect on transmitting activated signals upon LPS stimulation in macrophage. We found that c-FLIPL-expressing macrophage, Raw 264.7/c-FLIPL, could increase TNFα mRNA expression and TNFα secretion. The mechanism of enhancing secretion of TNFα was through the enhancement of adaptor protein, MyD88, then increased p38 phosphorylation under LPS stimulation. It is obviously c-FLIPL may transduce LPS-stimulated signal in macrophages. The results suggest that c-FLIPL could act as a valid pharmaceutical target for the treatment and prevention of chronic inflammatory diseases in health food or drug development.