小膠質細胞（microglia）是中樞神經系統的一種免疫巨噬細胞（macrophage），當中樞神經系統受損或發生神經退化性疾病，小膠質細胞會被活化，產生大量的前發炎因子（proinflammatory mediators），例如，一氧化氮（NO）、腫瘤壞死因子-α（TNF-α）及介白質素-1β（IL-1β）等等，擴大發炎反應，影響神經再生。神經滋養因子-3（NT-3）為一種神經滋養因子（neurotrophin），對於神經細胞存活及中樞神經系統發育扮演重要角色。受損的中樞神經系統中，活化的小膠質細胞會產生NT-3，同時也表現NT-3的受體，Trk C及p75NTR，然而，NT-3對活化小膠質細胞的作用卻未被深入探討。本研究中，藉由細菌脂多醣（LPS）活化BV2細胞株（一種小膠質細胞細胞株）及初級小膠質細胞，以探討NT-3對於小膠質細胞活化情形的影響。結果顯示以LPS活化小膠質細胞前24小時先處理NT-3，可顯著抑制誘導型一氧化氮合成酵素（iNOS）表現量、TNF-α及IL-1β產量；若NT-3與LPS同時處理或於LPS後處理小膠質細胞，則對小膠質細胞的活化沒有顯著的影響。進一步以Trk C的抑制劑K252a或MAPK的抑制劑U0126處理細胞，則前處理NT-3喪失對iNOS表現量的抑制效果；此外，NT-3前處理亦降低LPS誘導的NF-κB活化。推測NT-3經由與Trk C受體的結合，啟動細胞內MAPK訊息傳遞路徑，並抑制NF-κB的活化以降低iNOS及前發炎細胞激素的表現量。本研究結果顯示NT-3可明顯抑制小膠質細胞的活化，因此在中樞神經系統受損後，NT-3的產生不但有助於神經細胞的存活，更可作為一種抗發炎因子減緩損傷處的發炎反應。

Microglia, resident macrophages in the central nervous system (CNS), are activated in many CNS diseases, and act as important regulators for neuropathogenesis via producing proinflammatory mediators, such as nitric oxide (NO), TNF-α and IL-1β. Neurotrophin-3 (NT-3) is a well-known trophic factor for neural survival, development and plasticity. Activated microglia are NT-3-producing cells in the injured CNS, and express its receptor-Trk C and p75NTR. However, little is known about the effect of NT-3 on microglia. In this study, we investigated the effect of NT-3 on mouse microglia cell line (BV2) and primary rat microglia with stimulation of lipopolysaccharide (LPS). We found that 24h pre-treatment with NT-3 significantly suppressed the production of inducible NO synthetase (iNOS), NO, and TNF-α both in LPS-stimulated BV2 and primary rat microglia. Pretreatment with NT-3 also decreased the level of IL-1β in LPS-stimulated primary rat microglia. NT-3 had less effect on the reduction of these proinflammatory mediators when it was added to BV2 and primary microglia cultures either simultaneously with LPS or post LPS treatment. Similar results were found in primary rat microglia. Furthermore, we found that the inhibitory effect NT-3 on the production of microglial iNOS induced by LPS was abolished by K252a (TrkC inhibitor) and U0126 (MAPK inhibitor). Additionally, pretreatment with NT-3 also caused the inhibition of NF-κB activation in LPS-treated microglia. Our results suggest that NT-3 inhibited the production of iNOS and proinflammatory mediators by LPS-treated microglia through TrkC activation, MAPK signaling, and deactivation of NF-κB. Collectively, these results indicated that NT-3 may serve an anti-inflammatory factor to suppress microglial activation.

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