Butyrate Alleviates Cytokine-Induced Barrier Dysfunction by Modifying Claudin-2 Levels
Gastrointestinal (GI) disorders such as celiac disease and inflammatory bowel disease are attributed to intestinal barrier disruption. Imbalance of cytokines has been reported in the intestinal epithelium of patients with GI disorders. Short-chain fatty acids (SCFAs), derived from the fermentation o...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
|
| Series: | Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-7737/10/3/205 |
| _version_ | 1827698181163450368 |
|---|---|
| author | Xinyi Huang Tadayuki Oshima Toshihiko Tomita Hirokazu Fukui Hiroto Miwa |
| author_facet | Xinyi Huang Tadayuki Oshima Toshihiko Tomita Hirokazu Fukui Hiroto Miwa |
| author_sort | Xinyi Huang |
| collection | DOAJ |
| description | Gastrointestinal (GI) disorders such as celiac disease and inflammatory bowel disease are attributed to intestinal barrier disruption. Imbalance of cytokines has been reported in the intestinal epithelium of patients with GI disorders. Short-chain fatty acids (SCFAs), derived from the fermentation of dietary fiber in the intestine, have been reported to benefit the intestinal barrier. Accordingly, we evaluated the effect of specific SCFAs on intestinal barrier function under cytokine-stimulated conditions. Caco-2 cells were cultured on insert membranes to generate monolayers, which then were used to investigate the effects of SCFAs. Tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), or interleukin-13 (IL-13) was added to the basolateral side of the membrane while SCFAs were added to the apical side. After a 24 h stimulation, transepithelial electrical resistance (TEER) was measured, and the protein levels of claudin-1, claudin-2, claudin-3, claudin-4, occludin, and zonula occludens-1 (ZO-1) were evaluated by Western blot. Butyrate, but not acetate, propionate, or succinate, ameliorated the TNF-α/IFN-γ-induced decrease in TEER. TNF-α/IFN-γ stimulation significantly increased the protein level of claudin-2 and decreased the level of claudin-3. Butyrate significantly attenuated the upregulation of claudin-2 induced by TNF-α/IFN-γ. Butyrate blocked the decrease in TEER and the upregulation of claudin-2 induced by IL-13 without changing the level of other tight junction proteins. Our results suggested that butyrate is the main component of SCFAs to alleviate barrier dysfunction and that claudin-2 is the major target of this SCFA. |
| first_indexed | 2024-03-10T13:23:56Z |
| format | Article |
| id | doaj.art-294bbc9372a747a7bbd7a06ff73cd6c1 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T13:23:56Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-294bbc9372a747a7bbd7a06ff73cd6c12023-11-21T09:45:33ZengMDPI AGBiology2079-77372021-03-0110320510.3390/biology10030205Butyrate Alleviates Cytokine-Induced Barrier Dysfunction by Modifying Claudin-2 LevelsXinyi Huang0Tadayuki Oshima1Toshihiko Tomita2Hirokazu Fukui3Hiroto Miwa4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, JapanGastrointestinal (GI) disorders such as celiac disease and inflammatory bowel disease are attributed to intestinal barrier disruption. Imbalance of cytokines has been reported in the intestinal epithelium of patients with GI disorders. Short-chain fatty acids (SCFAs), derived from the fermentation of dietary fiber in the intestine, have been reported to benefit the intestinal barrier. Accordingly, we evaluated the effect of specific SCFAs on intestinal barrier function under cytokine-stimulated conditions. Caco-2 cells were cultured on insert membranes to generate monolayers, which then were used to investigate the effects of SCFAs. Tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), or interleukin-13 (IL-13) was added to the basolateral side of the membrane while SCFAs were added to the apical side. After a 24 h stimulation, transepithelial electrical resistance (TEER) was measured, and the protein levels of claudin-1, claudin-2, claudin-3, claudin-4, occludin, and zonula occludens-1 (ZO-1) were evaluated by Western blot. Butyrate, but not acetate, propionate, or succinate, ameliorated the TNF-α/IFN-γ-induced decrease in TEER. TNF-α/IFN-γ stimulation significantly increased the protein level of claudin-2 and decreased the level of claudin-3. Butyrate significantly attenuated the upregulation of claudin-2 induced by TNF-α/IFN-γ. Butyrate blocked the decrease in TEER and the upregulation of claudin-2 induced by IL-13 without changing the level of other tight junction proteins. Our results suggested that butyrate is the main component of SCFAs to alleviate barrier dysfunction and that claudin-2 is the major target of this SCFA.https://www.mdpi.com/2079-7737/10/3/205short-chain fatty acidsbutyrateclaudin-2intestinal barrier disruption |
| spellingShingle | Xinyi Huang Tadayuki Oshima Toshihiko Tomita Hirokazu Fukui Hiroto Miwa Butyrate Alleviates Cytokine-Induced Barrier Dysfunction by Modifying Claudin-2 Levels Biology short-chain fatty acids butyrate claudin-2 intestinal barrier disruption |
| title | Butyrate Alleviates Cytokine-Induced Barrier Dysfunction by Modifying Claudin-2 Levels |
| title_full | Butyrate Alleviates Cytokine-Induced Barrier Dysfunction by Modifying Claudin-2 Levels |
| title_fullStr | Butyrate Alleviates Cytokine-Induced Barrier Dysfunction by Modifying Claudin-2 Levels |
| title_full_unstemmed | Butyrate Alleviates Cytokine-Induced Barrier Dysfunction by Modifying Claudin-2 Levels |
| title_short | Butyrate Alleviates Cytokine-Induced Barrier Dysfunction by Modifying Claudin-2 Levels |
| title_sort | butyrate alleviates cytokine induced barrier dysfunction by modifying claudin 2 levels |
| topic | short-chain fatty acids butyrate claudin-2 intestinal barrier disruption |
| url | https://www.mdpi.com/2079-7737/10/3/205 |
| work_keys_str_mv | AT xinyihuang butyratealleviatescytokineinducedbarrierdysfunctionbymodifyingclaudin2levels AT tadayukioshima butyratealleviatescytokineinducedbarrierdysfunctionbymodifyingclaudin2levels AT toshihikotomita butyratealleviatescytokineinducedbarrierdysfunctionbymodifyingclaudin2levels AT hirokazufukui butyratealleviatescytokineinducedbarrierdysfunctionbymodifyingclaudin2levels AT hirotomiwa butyratealleviatescytokineinducedbarrierdysfunctionbymodifyingclaudin2levels |