乳酸菌Kefiranofaciens M1對於過敏性鼻炎和多元不飽和脂肪酸對於RBL-2H3細胞釋出發炎介質的影響

CLINICAL EFFICACY OF LACTOBACILLUS KEFIRANOFACIENS M1 ON ALLERGIC RHINITIS AND EFFECT OF POLYUNSATURATED FATTY ACIDS ON INFLAMMATORY MEDIATORS RELEASE BY RBL-2H3 CELLS

艾迪(Elkana Eddy Owaga)

指導教授 ： 謝榮鴻

臺北醫學大學/公共衛生暨營養學院/保健營養學研究所/博士(2014年)

https://doi.org/10.6831/TMU.2014.00029

摘要

None

關鍵字

None

並列摘要

The rapid rise in global prevalence of allergy disorders is a matter of public health concern. The pathogenesis of allergic rhinitis is associated with skewed T helper cells (Th1/Th2) immunobalance and subsequent sensitization of mast cells by allergen-specific immunoglobulin (IgE), which results in release of inflammatory mediators. Furthermore, activated mast cells undergo major metabolic reprogramming, primarily using glycolysis to support the effector functions upon allergen stimulation. Lactobacilli kefiranofaciens M1 (LKM1) has shown immunomodulation potential in cell and animal models, however, the safety and clinical effects on subjects with allergic rhinitis have not been elucidated. On the other hand, the modification role of dietary polyunsaturated fatty acids (PUFA) on the metabolism profile of activated mast cell and the implications on the release of inflammatory mediators are yet to be studied. In this thesis, we evaluated the efficacy of Lactobacillus kefiranofaciens M1 (LKM1) on allergic rhinitis in a randomized placebo-controlled trial, and polyunsaturated fatty acids (PUFA) on inflammatory mediator release by RBL-2H3 mast cells. In the toxicity assessment studies, LKM1 did not induce adverse effects on haematology, serum biochemistry, urinalysis, and organ histology safety variables in animal and human subjects. Furthermore, LKM1 administration did not result in marked improvement of the overall nasal cavity symptoms and sinonasal outcome test (SNOT) quality-of-life scores. However, importantly, LKM1 selectively relieved some aspects including nasal cavity mucosal color and facial pain SNOT variables, and the associated underlying mechanism may involve suppressed secretion of IL-6, an important Th2 cytokine in the induction of allergic rhinitis symptoms. In the PUFA study, we examined the modulatory effects of PUFA including arachidonic acid (AA), docosahexanoic acid (DHA), α-linolenic acid (ALA) and linoleic acid (LA) on the bioenergetic profile of house dust mite (HDM)-stimulated RBL-2H3 mast cell line and the implication on histamine secretion and gene expression of pro-inflammatory cytokines (IL-4, IL-6, IL-13, TNF-α mRNA) as well as the underlying bioenergetic mechanisms. The data showed α-linolenic acid (an n-3 PUFA) inhibited IL-4 mRNA expression in a mitochondria complex-1 dependent manner, and the bioenergetic mechanisms may involve enhanced mitochondrial spare respiratory capacity via increased mitochondria DNA copy number, mitochondria membrane potential, and antioxidant enzymes activities (catalase and glutathione peroxidase). In addition, ALA suppressed the expression of mammalian target of rapamycin (mTOR) mRNA, an important transcription regulator of aerobic glycolysis during growth and proliferation of activated mast cells. In conclusion, the findings of this thesis underscores the potential novel role of dietary Lactobacilli kefiranofaciens M1 and α-linolenic acid in the prevention of allergy-related inflammation through immunomodulation and cellular bioenergetics mechanisms, respectively.

並列關鍵字

Lactobacillus kefiranofaciens M1, allergic rhinitis, polyunsaturated fatty acids, histamine, cytokines, mast cells

參考文獻

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