人類被沙門氏菌感染的表現徵狀通常是產生腹瀉的小腸結腸炎，伴隨著腸道表皮細胞被刺激分泌促炎性細胞因子 (pro-inflammatory cytokine)，同時會有嗜中性粒細胞滲透入腸粘膜下層的現象， 是為腸道發炎的特徵。將嗜中性粒細胞從循環系統招集到皮膜下區域是由像白細胞介素-8 (Interleukin-8, IL-8) 之類的細胞趨化因子所驅動的，而IL-8是已知在表皮細胞被細菌侵入時會被大量誘發的因子。
益生菌能被用以預防或治癒某些形式的炎性腸病 (Inflammatory Bowel Disease, IBD)。某些乳桿菌屬中的菌種能成功的達成調節促發炎性細胞因子的細胞訊息傳遞，進而發揮在腸胃道裡降發炎的作用。
在這項研究中， 我們使用人類腸道細胞株HCT 116來模擬腸道表皮細胞，並用人類白血病化單核球細胞株THP-1來模擬血球細胞系統 ， 用以探討四株乳桿菌屬的益生菌對於被沙門氏菌感染而引起發炎的細胞施加的效果。這項研究所用以感染細胞的沙門氏菌是野生型SL1344，為了使其盡量呈現具有侵入細胞的能力的表型而將其在無氧條件下培養到成長(指數)期晚期。我們所使用的四株益生菌分別為嗜酸乳酸菌(Lactobacillus acidophilus)、鼠李糖乳桿菌(Lactobacillus rhamnosus)、副乾酪乳桿菌 (Lactobacillus paracasei)、德氏乳桿菌(Lactobacillus delbrueckii)。
結果顯示四株益生菌皆能對所測試的三個發炎相關細胞因子之mRNA表現量發揮到某程度調節降低的作用，但是效果是偶發而不一致的。唯獨副乾酪乳桿菌(Lactobacillus paracasei)這一株能反覆並可靠地抑制IL-8之mRNA表現。 我們的實驗結果透過感染測試顯示了腸道表皮細胞被沙門氏菌感染時最劇烈的反應是IL-8表現量的調升，顯示了細胞被細菌感染而發炎可能與細胞中IL-8表現的上調有關聯。 但是， 在侵入細胞的細菌數定量結果顯示副乾酪乳桿菌並未明顯減少細胞內的細菌數， 反而是鼠李糖乳桿菌 (Lactobacillus rhamnosus)這一株益生菌達到了顯著減少細胞被細菌侵入的效果。這些發現顯示了不同種類的益生菌或許透過不同的機制發揮降發炎的作用，以及鼠李糖乳桿菌似乎能保護腸道表皮細胞使之較不易被沙門氏菌侵入。

Salmonella infection in humans is commonly manifested as enterocolitis characterized by induction of epithelial secretion of pro-inflammatory cytokines and diarrhea, accompanied by infiltration of neutrophils in the intestinal submucosa, which is a hall-mark of intestinal inflammation. The recruitment of neutrophils from circulation to the subepithelial region is facilitated by chemokines such as interleukin-8 (IL-8), which is known to be significantly induced upon bacterial entry by host epithelial cells.
Probiotics are able to be used in the prevention or treatment of certain types of in-flammatory bowel disease (IBD). Certain types of Lactobacillus strains are successful in modulating pro-inflammatory cytokine signaling, which in turn, reduce inflammation in the gastrointestinal tract.
In this study, we used the human intestinal cell line HCT 116 as an intestinal epithelial model, and the human leukemic monocyte cell line THP-1 as a leukocyte model, to determine the effects of four arbitrarily chosen strains of Lactobacillus probiotics on inflammation caused by Salmonella infection. The Salmonella strain used in the study is the wild-type SL1344, grown under anaerobic conditions to late log phase to maximize invasion phenotype. The four probiotic strains are Lactobacillus acidophilus, Lactoba-cillus rhamnosus, Lactobacillus paracasei, and Lactobacillus delbrueckii.
Our results show that all four strains of probiotics were able to sporadically reduce mRNA expression of the three tested cytokines, but only Lactobacillus paracasei was able to consistently lower IL-8 expression. Our experimental results had shown in infection tests that upon Salmonella infection, the most acute response is seen in the upregu-lation of IL-8 expression, suggesting a possible relation between inflammation induced by bacterial infection and IL-8 induction. However, invasion assays show that Lactoba-cillus paracasei did not significantly reduce the amount of intracellular bacteria. In-stead, only Lactobacillus rhamnosus, which did not consistently suppress IL-8, signifi-cantly reduced bacterial invasion. These findings suggest that various probiotics sup-press inflammation through different mechanisms, and that the probiotic Lactobacillus rhamnosus is able to protect intestinal epithelial cells by rendering them less suscepti-ble to Salmonella invasion.

論文審定書…………………………………………………………… i
誌謝…………………………………………………………………… ii
中文摘要……………………………………………………………… iii
英文摘要 (Abstract)………………………………………………… v
圖次 (Figures)……………………………………………………… iix
縮寫與符號說明 (Abbreviations & Notations)……………………… ix
緒論 (Introduction)…………………………………………………… 10
Materials & Methods………………………………………………… 16
結果 (Results)………………………………………………………… 21
討論 (Discussion)…………………………………………………… 24
參考文獻 (References)……………………………………………… 45
附錄(Appendix)……………………………………………………… 53

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