Treatment with phenylbutyrate in a pre-clinical trial reduces diarrhea due to enteropathogenic Escherichia coli: link to cathelicidin induction

被引：29

作者：

Al-Mamun, Abdullah ^{[1
]}

Mily, Akhirunnessa ^{[1
]}

Sarker, Protim ^{[1
]}

Tiash, Snigdha ^{[1
]}

Navarro, Armando ^{[2
]}

Akter, Mahmuda ^{[1
]}

Talukder, Kaisar Ali ^{[1
]}

Islam, Mohammad Faizul ^{[1
]}

Agerberth, Birgitta ^{[3
]}

Gudmundsson, Gudmundur H. ^{[4
,5
]}

Cravioto, Alejandro ^{[1
]}

Raqib, Rubhana ^{[1
]}

机构：

[1] Int Ctr Diarrhoeal Dis Res, Dhaka 1212, Bangladesh

[2] Univ Nacl Autonoma Mexico, Fac Med, Dept Salud Publ, Mexico City 04510, DF, Mexico

[3] Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden

[4] Univ Iceland, Inst Biol, IS-101 Reykjavik, Iceland

[5] Univ Iceland, Biomed Ctr, IS-101 Reykjavik, Iceland

来源：

MICROBES AND INFECTION | 2013年 / 15卷 / 13期

基金：

瑞典研究理事会;

关键词：

EPEC; Diarrhea; Antimicrobial peptide; CAP-18; Phenylbutyrate; Small intestine; ANTIMICROBIAL PEPTIDE LL-37; CHAIN FATTY-ACIDS; VIBRIO-CHOLERAE; SHIGELLOSIS; EXPRESSION; INFECTION; INFANTS; INFLAMMATION; PATHOGENESIS; INVOLVEMENT;

D O I：

10.1016/j.micinf.2013.08.007

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Treatment of shigellosis in rabbits with phenylbutyrate reduces clinical severity and counteracts down-regulation of cathelicidin (CAP-18) in the large intestinal epithelia. We aimed to further evaluate whether in a rabbit model of enteropathogenic Escherichia coli (EPEC) diarrhea, CAP-18 is down-regulated in the small intestine and if oral phenylbutyrate treatment affects CAP-18 expression, clinical recovery, shedding of EPEC in stool and virulence properties of the isolated colonies. EPEC-induced diarrhea down-regulated CAP-18 in the small intestinal epithelia as revealed by immunohistochemistry. Phenylbutyrate treatment reduced clinical illness, improved histological features of inflammation and upregulated CAP-18 in the epithelia. Active CAP-18 peptide was also released in the stool as noted in Western blot analysis. Multiplex PCR analysis of total bacterial DNA in the stool showed absence of EPEC specific genes eae and bfpA. Treated rabbits shed rough strains still harboring eae and bfpA genes, which were less potent in binding to HeLa cells and induced delayed onset of diarrhea in new rabbits. In conclusion, EPEC-mediated down-regulation of CAP-18 in the small intestinal epithelia was restored by phenylbutyrate treatment. Upregulation of CAP-18 in the epithelia was accompanied by healing of the epithelial lining, reduced shedding and virulence of EPEC and recovery from diarrhea. (C) 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

引用

页码：939 / 950

页数：12

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