USING A CACO-2 AND THP-1 CO-CULTURE MODEL TO EVALUATE INTESTINAL BARRIER PROTECTIVE PROPERTIES — EFFECTS OF DEXAMETHASONE Article Swipe
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· 2022
· Open Access
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· DOI: https://doi.org/10.15605/jafes.037.afes.04
OBJECTIVES Increased intestinal permeability or so-called “leaky gut,” is considered an early event in the development of obesity and diabetes. It is likely driven by the translocation of bacteria-derived products such as lipopolysaccharide (LPS) from the intestinal lumen into the blood stream leading to low-grade inflammation. A co-culture model of intestinal barrier dysfunction was used to characterize the mechanisms of barrier protection induced by an anti-inflammatory drug METHODOLOGY In co-cultured CACO-2 and THP-1 cells representing the intestinal epithelium and immune cells, respectively, barrier dysfunction was induced using LPS and quantified by measuring trans-epithelial electrical resistance (TEER). Dexamethasone was tested for its barrier-protective properties by application to the apical side. Dexamethasone concentration was quantified on apical and basolateral sides after 24-hour treatment using liquid chromatography/mass spectrometry. Cytokine release was determined using a multiplex chemiluminescence assay (mesoscale discovery). Expression of selected tight junction (TJ) proteins was assessed using immunocytochemical staining and confocal imaging. RESULTS Dexamethasone significantly (p=0.009) improved TEER by 30%, while 74% of the dexamethasone remained on the apical side and 24% was detected basolaterally. Dexamethasone significantly decreased interleukin (IL)-6 (p<0.0001), tumour necrosis factor α (p<0.0001) and IL-1β (p=0.051) release by THP-1 cells. However, confocal imaging revealed that dexamethasone did not improve the localization of occludin, claudin-2 or zonula occludens-1 when compared to LPS-induced cells. CONCLUSION Dexamethasone improved barrier function likely due to its anti-inflammatory effect. However, it could not prevent localization of the pore-forming claudin-2, which may explain the presence of residual barrier dysfunction in this model.
Related Topics
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.15605/jafes.037.afes.04
- https://asean-endocrinejournal.org/index.php/JAFES/article/download/5827/4959
- OA Status
- diamond
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412010328
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4412010328Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.15605/jafes.037.afes.04Digital Object Identifier
- Title
-
USING A CACO-2 AND THP-1 CO-CULTURE MODEL TO EVALUATE INTESTINAL BARRIER PROTECTIVE PROPERTIES — EFFECTS OF DEXAMETHASONEWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-10-14Full publication date if available
- Authors
-
Sylvia Riedel, Lize Engelbrecht, Pieter Venter, Johan Louw, Carmen Pheiffer, Christo J. F. MullerList of authors in order
- Landing page
-
https://doi.org/10.15605/jafes.037.afes.04Publisher landing page
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https://asean-endocrinejournal.org/index.php/JAFES/article/download/5827/4959Direct link to full text PDF
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YesWhether a free full text is available
- OA status
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diamondOpen access status per OpenAlex
- OA URL
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https://asean-endocrinejournal.org/index.php/JAFES/article/download/5827/4959Direct OA link when available
- Concepts
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Medicine, Dexamethasone, THP1 cell line, Caco-2, Internal medicine, In vitro, Cell culture, Biochemistry, Chemistry, Genetics, BiologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.OBJECTIVES | 0 |
| abstract_inverted_index.claudin-2, | 234 |
| abstract_inverted_index.co-culture | 47 |
| abstract_inverted_index.considered | 9 |
| abstract_inverted_index.determined | 128 |
| abstract_inverted_index.electrical | 93 |
| abstract_inverted_index.epithelium | 77 |
| abstract_inverted_index.intestinal | 2, 36, 50, 76 |
| abstract_inverted_index.mechanisms | 58 |
| abstract_inverted_index.properties | 102 |
| abstract_inverted_index.protection | 61 |
| abstract_inverted_index.quantified | 89, 112 |
| abstract_inverted_index.resistance | 94 |
| abstract_inverted_index.LPS-induced | 212 |
| abstract_inverted_index.METHODOLOGY | 67 |
| abstract_inverted_index.application | 104 |
| abstract_inverted_index.basolateral | 116 |
| abstract_inverted_index.co-cultured | 69 |
| abstract_inverted_index.development | 15 |
| abstract_inverted_index.discovery). | 135 |
| abstract_inverted_index.dysfunction | 52, 83, 243 |
| abstract_inverted_index.interleukin | 177 |
| abstract_inverted_index.occludens-1 | 208 |
| abstract_inverted_index.characterize | 56 |
| abstract_inverted_index.localization | 202, 230 |
| abstract_inverted_index.permeability | 3 |
| abstract_inverted_index.pore-forming | 233 |
| abstract_inverted_index.representing | 74 |
| abstract_inverted_index.(p<0.0001) | 184 |
| abstract_inverted_index.Dexamethasone | 96, 109, 152, 174, 215 |
| abstract_inverted_index.concentration | 110 |
| abstract_inverted_index.dexamethasone | 163, 197 |
| abstract_inverted_index.inflammation. | 45 |
| abstract_inverted_index.respectively, | 81 |
| abstract_inverted_index.significantly | 153, 175 |
| abstract_inverted_index.spectrometry. | 124 |
| abstract_inverted_index.translocation | 26 |
| abstract_inverted_index.(p<0.0001), | 179 |
| abstract_inverted_index.basolaterally. | 173 |
| abstract_inverted_index.bacteria-derived | 28 |
| abstract_inverted_index.trans-epithelial | 92 |
| abstract_inverted_index.anti-inflammatory | 65, 223 |
| abstract_inverted_index.chemiluminescence | 132 |
| abstract_inverted_index.barrier-protective | 101 |
| abstract_inverted_index.immunocytochemical | 146 |
| abstract_inverted_index.lipopolysaccharide | 32 |
| abstract_inverted_index.chromatography/mass | 123 |
| cited_by_percentile_year | |
| countries_distinct_count | 0 |
| institutions_distinct_count | 6 |
| citation_normalized_percentile.value | 0.30045824 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |