Iba Hitomi, Shimohata Takaaki, Kido Junko, Hatayama Sho, Uebanso Takashi, Mawatari Kazuaki, Takahashi Akira
Department of Preventive Environment and Nutrition, Institute of Biomedical Sciences, Tokushima University, Tokushima Japan.
Department of Health and Nutrition, Nagasaki International University Nagasaki Japan.
J Med Invest. 2021;68(1.2):59-70. doi: 10.2152/jmi.68.59.
Vibrio parahaemolyticus is a foodborne bacterium that causes acute gastroenteritis through the consumption of contaminated, raw, or undercooked seafood. Cystic fibrosis transmembrane conductance regulator (CFTR) is a well-characterized chloride channel that regulates several other ion channels and transporters to maintain water homeostasis in the gut lumen. Also, CFTR is a main target of bacterial infection-associated diarrhea. Hence, the aim of this study was to clarify the contribution of CFTR in V. parahaemolyticus-induced diarrhea in a mouse model of intestinal loop fluid accumulation, with CFTR inhibitors and a CFTR knockout model. The results indicated that CFTR plays a critical role in fluid accumulation in response to V. parahaemolyticus infection. We also investigated the inflammatory association in CFTR-mediated V. parahaemolyticus-induced fluid secretion with cyclooxygenase inhibitors and found that fluid accumulation was decreased by inhibition of cyclooxygenase 2 produced by neutrophils. These findings suggest that V. parahaemolyticus-inducing infiltration and activation of neutrophils also participated in CFTR mediated fluid secretion. This study reveals an important relationship between V. parahaemolyticus-induced diarrhea and inflammation in a mouse model. J. Med. Invest. 68 : 59-70, February, 2021.
副溶血性弧菌是一种食源性细菌,通过食用受污染的生的或未煮熟的海鲜导致急性肠胃炎。囊性纤维化跨膜传导调节因子(CFTR)是一种特征明确的氯离子通道,它调节其他几种离子通道和转运体,以维持肠腔内的水平衡。此外,CFTR是细菌感染相关性腹泻的主要靶点。因此,本研究的目的是利用CFTR抑制剂和CFTR基因敲除模型,在肠袢液体蓄积的小鼠模型中阐明CFTR在副溶血性弧菌诱导的腹泻中的作用。结果表明,CFTR在副溶血性弧菌感染引起的液体蓄积中起关键作用。我们还用环氧化酶抑制剂研究了CFTR介导的副溶血性弧菌诱导的液体分泌中的炎症关联,发现抑制中性粒细胞产生的环氧化酶2可减少液体蓄积。这些发现表明,副溶血性弧菌诱导的中性粒细胞浸润和激活也参与了CFTR介导的液体分泌。本研究揭示了小鼠模型中副溶血性弧菌诱导的腹泻与炎症之间的重要关系。《医学调查杂志》2021年2月第68卷:59 - 70页