The Role of Hyaluronan in Innate Host Defense against Bacterial Infection

Bibliographic Details
Main Author:	Kim, Yeojung
Language:	English
Published:	Case Western Reserve University School of Graduate Studies / OhioLINK 2017
Subjects:	Biomedical Research Cellular Biology Microbiology Molecular Biology
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=case1499340461710323

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-case14993404617103232021-08-03T07:03:09Z The Role of Hyaluronan in Innate Host Defense against Bacterial Infection Kim, Yeojung Biomedical Research Cellular Biology Microbiology Molecular Biology Homeostasis in the intestinal tract is maintained by balancing between a constant microbial challenge and the innate host defense. Once this balance is disrupted, resulting either from the thinning of the mucus layer, insufficient expression of antimicrobial peptides, or loosening of the tight junctions between the intestinal epithelial cells, microbes may invade into the intestinal mucosa. Microbial invasion leads to infection and induction of proinflammatory responses. Together, these factors may promote development of diseases such as inflammatory bowel disease (IBD) and necrotizing colitis (NEC). Therefore, sustaining a functional innate host defense is critical for the prevention of bacterial infections in the gut. Beneficial effects from breast-feeding are known to prevent the development of multiple infectious diseases including NEC in infants. Hyaluronan (HA), a linear polysaccharide, is a natural product and present in breast milk. Studies have shown that specific sized HA 35 kDa (HA35) can mimic the effect of HA in human milk. However, the known effect of HA35 on intestinal epithelium has been limited to the induction of antimicrobial peptides. We found that HA35 treatment protects mice from Citrobacter rodentium infection, a model of enteropathogenic E.coli infection in humans. Citrobacter, an attaching and effacing bacteria,passes between epithelial cells during infection. We hypothesized that HA35 treatment modulates junction proteins to tighten the epithelial barrier and prevent bacterial infection. Notably, HA35 treatment was found to increase the expression of tight junction protein zonula occludens-1 (ZO-1) in vitro and in vivo. In healthy mice, ZO-1 was induced only in the distal colon but in the mice with early stage of dextran sulfate sodium (DSS)-induced colitis, ZO-1 was induced in both transverse and distal colons with reduced intestinal permeability. Furthermore, layilin, an unusual HA receptor, mediated increased ZO-1 expression post HA35 treatment in mouse intestinal epithelium in vitro and in vivo. Finally, ZO-1 expression was reduced in IBD patients, while layilin expression was equivalent in IBD and non-IBD patients, supporting the concept that oral HA35 treatment may be a safe prophylactic treatment for IBD patients. 2017-09-06 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1499340461710323 http://rave.ohiolink.edu/etdc/view?acc_num=case1499340461710323 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Biomedical Research Cellular Biology Microbiology Molecular Biology
spellingShingle	Biomedical Research Cellular Biology Microbiology Molecular Biology Kim, Yeojung The Role of Hyaluronan in Innate Host Defense against Bacterial Infection
author	Kim, Yeojung
author_facet	Kim, Yeojung
author_sort	Kim, Yeojung
title	The Role of Hyaluronan in Innate Host Defense against Bacterial Infection
title_short	The Role of Hyaluronan in Innate Host Defense against Bacterial Infection
title_full	The Role of Hyaluronan in Innate Host Defense against Bacterial Infection
title_fullStr	The Role of Hyaluronan in Innate Host Defense against Bacterial Infection
title_full_unstemmed	The Role of Hyaluronan in Innate Host Defense against Bacterial Infection
title_sort	role of hyaluronan in innate host defense against bacterial infection
publisher	Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate	2017
url	http://rave.ohiolink.edu/etdc/view?acc_num=case1499340461710323
work_keys_str_mv	AT kimyeojung theroleofhyaluronanininnatehostdefenseagainstbacterialinfection AT kimyeojung roleofhyaluronanininnatehostdefenseagainstbacterialinfection
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The Role of Hyaluronan in Innate Host Defense against Bacterial Infection

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