麩醯胺對於肺部發炎反應免疫調節之影響

免疫防禦能力於維持呼吸系統之健康扮演相當重要的角色，當病原菌入侵呼吸道時，會誘發呼吸道上皮細胞nuclear factor (NF)-κB之活化，促進CXC化學趨化因子生成，吸引嗜中性白血球聚集至發炎部位清除病源，而發炎之緩解則受到調節型T細胞(regulatory T cell, Treg)所調控。肺臟是維持體內麩醯胺(glutamine, GLN)恆定的重要器官，而GLN為臨床上常用之免疫調節營養素，本研究利用細胞實驗探討GLN對呼吸道上皮細胞NF-κB活化之影響，並利用急性肺損傷(acute lung injury, ALI)動物模式，探討GLN對於緩解肺部發炎反應之影響。研究結果發現，GLN透過Akt/mTOR/IKKβ之途徑，抑制lipopolysaccharide (LPS)誘發人類支氣管上皮細胞株BEAS-2B細胞NF-κB之活化。GLN降低NF-κB之轉錄能力，減少NF-κB目標基因的表現，而生理濃度GLN (0.5 mM)對NF-κB之抑制效果最好。動物實驗以LPS引致C57BL/6J小鼠肺損傷一天之後，每天灌食0.5 g GLN/kg BW，連續9天，給予GLN可增加肺泡灌洗液中Treg之比率，進而促進嗜中性白血球之清除；並抑制輔助型T細胞(helper T cells, Th cells)表現interleukin-17，緩解肺部之發炎反應。本研究結果顯示，GLN透過調節先天性和後天性免疫反應減緩呼吸道之發炎，可提供臨床上ALI病人使用GLN營養介入之參考。

關鍵字

麩醯胺；脂多醣； NF-κB ； mTOR ；急性肺損傷；發炎之緩解；調節型T細胞

並列摘要

Immune defense system plays a critical role in maintaining the health of respiratory functions. In the presence of microorganisms, airway epithelial cells provoke inflammatory responses mediated by nuclear factor (NF)-κB. Activation of NF-κB promotes production of CXC chemokines that leads to neutrophil recruitment to eliminate pathogens invaded into lungs. T helper (Th) cells modulate lung inflammatory reaction and regulatory T cells (Tregs) participate in the resolution of inflammation. The lungs are an important organ for glutamine (GLN) homeostasis and GLN is a nutrient commonly used in immunonutrition regimens. This study investigated the effects of GLN on activation of NF-κB in BEAS-2B cell line derived from human bronchial epithelial cells. Also, the possible roles of GLN on resolution of inflammation in a murine model of acute lung injury (ALI) were studied. The results showed that GLN modulated lipopolysaccharide (LPS)-induced activation of NF-κB through the Akt/mTOR/IKKβ pathway in BEAS-2B cells. GLN administration decreased the transcriptional activity of NF-κB, which suppressed the expression of NF-κB-targeted genes. Physiological concentration of GLN (0.5 mM) had a greater extent of inhibition on the NF-κB signaling cascade. In the animal study, LPS was instilled intratracheally 1 day after ALI. Then the C57BL/6J mice were gavaged with 0.5 g GLN/kg BW daily for subsequent 9 days. The results found that GLN resolved lung inflammation by increasing the population of Tregs in bronchoalveolar lavage fluid which promoted neutrophil clearance, and suppressed the expression of interleukin-17. This study indicated that GLN attenuated pulmonary inflammation at least partly by modulating both innate and adaptive immune responses. The findings imply that GLN can be considered as a nutritional supplement for ALI patients.

並列關鍵字

glutamine ； lipopolysaccharide ； NF-κB ； mTOR ； acute lung injury ； resolution of inflammation ； Treg

參考文獻

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麩醯胺對於肺部發炎反應免疫調節之影響

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