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Curcumin Ameliorates Hydrogen Peroxide-Induced Epithelial Barrier Disruption by Upregulating Heme Oxygenase-1 Expression in Human Intestinal Epithelial Cells

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Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Disruption of epithelial tight junctions (TJ) followed by loss of barrier function is of crucial importance in the pathogenesis of a variety of gastrointestinal disorders. Heme oxygenase-1 (HO-1), which can be induced by curcumin (Cur), provides protection against various forms of oxidative stress.

Aims

The protective effect of Cur on oxidative stress-induced intestinal barrier disruption in human intestinal epithelial cells was elucidated in this study.

Methods

H2O2-induced Caco-2 enterocytic monolayers were incubated in the presence or absence of Cur and/or zinc protoporphyrin (ZnPP). The trans-epithelial electrical resistance (TEER) and the flux of sodium fluorescein in the filter-grown Caco-2 cell monolayers were measured. The expression and localization of the TJ protein occludin and zonula occluden-1 (ZO-1) were evaluated by western blot and immunofluorescence microscopy. The mRNA and protein levels of HO-1 were analyzed by real-time PCR and western blot.

Results

Cur attenuated H2O2-induced disruption of paracellular permeability (TEER 52.02 ± 10.15% vs 22.71 ± 3.11%; sodium fluorescein flux 12.41 ± 2.19% vs 32.00 ± 4.97%, P < 0.05) and induced HO-1 mRNA (6.64 ± 0.48 vs 3.22 ± 0.28, P < 0.05) and protein (291.00 ± 9.17% vs 99.00 ± 10.00%, P < 0.05) expression in Caco-2 cells. After administration of H2O2, occludin and ZO-1 proteins were restored by Cur (occludin 175.67 ± 29.50% vs 53.67 ± 24.19%, P < 0.05; ZO-1 139.67 ± 33.71% vs 36.00 ± 15.88%, P < 0.05) and this effect was blocked by HO-1 inhibitor, ZnPP (occludin 54.67 ± 10.02% vs 168.33 ± 36.47%, P < 0.05; ZO-1 50.00 ± 15.13% vs 117.67 ± 38.81%, P < 0.05).

Conclusion

Cur protects human intestinal epithelial cells against H2O2-induced disruption of TJ and barrier dysfunction via the HO-1 pathway.

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Abbreviations

TJ:

Tight junction

OJ:

Obstructive jaundice

IBD:

Inflammatory bowel disease

AP:

Acute pancreatitis

Cur:

Curcumin

AJ:

Adhere junctions

JAM:

Junctional adhesion molecule

ZOs:

Zonula occludens

H2O2 :

Hydrogen peroxide

HO-1:

Heme oxygenase-1

DMEM:

Dulbecco’s Vogt modified Eagle’s media

TEER:

Trans-epithelial electrical resistance

ZnPP:

Zinc protoporphyrin

LDH:

Lactate dehydrogenase

MDA:

Malondialdehyde

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Acknowledgments

This work was supported in part by a grant to Huiqing Jiang from the National Natural Science Foundation of China (no. 81170411), the Natural Science Foundation of Hebei Province, China (no. C2010000530), and the Health Department Foundation of Hebei Province, China (no. 20090377).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Gastroenterology, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei Province, China

    Na Wang, JingXia Hao, JunJi Ma, Yan Wang & HuiQing Jiang

  2. Pediatric Intensive Care Unit, Baoding Children’s Hospital, Baoding, Hebei Province, China

    Gai Wang

  3. Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, USA

    XiaoYu Jiang

Authors
  1. Na Wang
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  2. Gai Wang
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  3. JingXia Hao
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  4. JunJi Ma
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  5. Yan Wang
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  7. HuiQing Jiang
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Corresponding author

Correspondence to HuiQing Jiang.

Additional information

Na Wang and Gai Wang contributed equally to this work.

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Wang, N., Wang, G., Hao, J. et al. Curcumin Ameliorates Hydrogen Peroxide-Induced Epithelial Barrier Disruption by Upregulating Heme Oxygenase-1 Expression in Human Intestinal Epithelial Cells. Dig Dis Sci 57, 1792–1801 (2012). https://doi.org/10.1007/s10620-012-2094-7

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  • DOI: https://doi.org/10.1007/s10620-012-2094-7

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