scholarly journals Doxorubicin increases permeability of murine small intestinal epithelium and cultured T84 monolayers

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Paul Cray ◽  
Breanna J. Sheahan ◽  
Jocsa E. Cortes ◽  
Christopher M. Dekaney

AbstractEnteric bacteria and/or their products are necessary for doxorubicin (DXR)-induced small intestine mucosal damage. While DXR does not induce gross loss of epithelium, others have shown elevated serum endotoxin after DXR administration. However, the mechanism of movement is unknown. We hypothesized that DXR treatment resulted in increased paracellular translocation of bacteria or bacterial products through the small intestinal epithelium. We measured permeability after DXR administration using transepithelial resistance and macromolecular flux and assessed tight junctional gene expression and protein localization both in vitro using T84 cells and ex vivo using murine jejunum. DXR treatment increased flux of 4 kDa dextrans in mouse jejenum, but increased flux of 4, 10 and 20 kDa dextrans in T84 cells. Following DXR, we observed increased permeability, both in vitro and ex vivo, independent of bacteria. DXR induced increased expression of Cldn2 and Cldn4 in murine small intestine but increased only CLDN2 expression in T84 cells. DXR treatment induced disorganization of tight junctional proteins. We conclude that DXR increases paracellular transit of small macromolecules, including bacterial products, through the epithelium, by altering expression of tight junctional components and dynamic loosening of cellular tight junctions.

Animals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 870
Author(s):  
Haihan Zhang ◽  
Dongfeng Li ◽  
Lingbin Liu ◽  
Ling Xu ◽  
Mo Zhu ◽  
...  

The small intestine plays an important role for animals to digest and absorb nutrients. The epithelial lining of the intestine develops from the embryonic endoderm of the embryo. The mature intestinal epithelium is composed of different types of functional epithelial cells that are derived from stem cells, which are located in the crypts. Chickens have been widely used as an animal model for researching vertebrate embryonic development. However, little is known about the molecular basis of development and differentiation within the chicken small intestinal epithelium. This review introduces processes of development and growth in the chicken gut, and compares the cellular characteristics and signaling pathways between chicken and mammals, including Notch and Wnt signaling that control the differentiation in the small intestinal epithelium. There is evidence that the chicken intestinal epithelium has a distinct cellular architecture and proliferation zone compared to mammals. The establishment of an in vitro cell culture model for chickens will provide a novel tool to explore molecular regulation of the chicken intestinal development and differentiation.


2013 ◽  
Vol 19 (12) ◽  
pp. 961-969 ◽  
Author(s):  
Ziyad Jabaji ◽  
Connie M. Sears ◽  
Garrett J. Brinkley ◽  
Nan Ye Lei ◽  
Vaidehi S. Joshi ◽  
...  

Author(s):  
Zhongyuan Guo ◽  
Glen DeLoid ◽  
Xiaoqiong Cao ◽  
Dimitrios Bitounis ◽  
Kaarunya Sampathkumar ◽  
...  

Nanoscale materials derived from natural biopolymers like cellulose and chitosan have many potentially useful agri-food and oral drug delivery applications. Because of their large and potentially bioactive surface areas and...


2021 ◽  
pp. 112609
Author(s):  
Glen M. DeLoid ◽  
Xiaoqiong Cao ◽  
Dimitrios Bitounis ◽  
Dilpreet Singh ◽  
Paula Montero Llopis ◽  
...  

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 12-13
Author(s):  
H D Nguyen ◽  
A Stadnyk

Abstract Background IL-10 is appreciated for its potent anti-inflammatory effects on leukocytes in mucosal immunity. However, far less attention has been paid to the impact of IL-10 on epithelial cells, which make up the crucial barrier interface between the host mucosa and the external environment. Furthermore, most studies examine the effects of exogenous IL-10, disregarding the possible presence and function of autocrine or paracrine IL-10 in the epithelium. Aims Using ex vivo organoids we aimed to examine the small intestinal epithelium for IL-10 and dissect any role for endogenously produced cytokine. Methods We growed small intestinal organoids (enteroids) from crypts isolated from C57BL/6 mice (WT) and IL-10-gene knockout mice (IL-10KO). Cellular markers were characterized through qpCR, while IL-10 and IL-10 receptor localization was characterized though immunofluorescence. Results We discovered that cells in WT enteroids expressed IL-10 and IL-10R1 constitutively throughout development. Immunofluorescent staining revealed that IL-10 localizes to Paneth cells and appears to be secreted apically. Having established that IL-10 is secreted in enteroids, we compared enteroids from IL-10KO versus WT mice. IL-10KO enteroids developed to morphologically resemble WT enteroids; however, we detected an imbalance with lower secretory cell markers over absorptive cell types in the IL-10KO enteroids, measured as less mRNA for lysozyme, cryptdins and mucin-2. Addition of IL-10 to IL-10KO enteroids did not correct these defects, but did ameliorate the lineage balance by reducing absorptive cell lineage markers (sucrose isomaltase). IL-10R1 was localized on both apical and basolateral side of cell in enteroids. We suspect that epithelial-derived IL-10 likely acts on apical IL-10R, which may conduct a different response from basolateral receptor stimulation. Conclusions In conclusion, IL-10 is present in the small intestinal epithelium; more remains to be determined regarding the role this cytokine plays in gut development and homeostasis. Funding Agencies NSERC


Sign in / Sign up

Export Citation Format

Share Document