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Blockade of hypoxia-inducible factor-1α by YC-1 attenuates interferon-γ and tumor necrosis factor-α-induced intestinal epithelial barrier dysfunction.
Cytokine. 2011 Dec; 56(3):581-8.C

Abstract

Proinflammatory cytokines play vital roles in intestinal barrier function disruption. YC-1 has been reported to have potent anti-inflammatory properties, and to be a potential agent for sepsis treatment. Here, we investigated the protective effect of YC-1 against intestinal barrier dysfunction caused by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). To assess the protective effect of YC-1 on intestinal barrier function, Caco-2 monolayers treated with simultaneous IFN-γ and TNF-α were used to measure transepithelial electrical resistance (TER) and paracellular permeability. To determine the mechanisms involved in the protective action of YC-1, expression and distribution of tight junction proteins ZO-1 and occludin in Caco-2 monolayers challenged with simultaneous IFN-γ and TNF-α were analyzed by Western blot and immunofluorescence, respectively. Expressions of phosphorylated myosin light chain (MLC), MLC kinase (MLCK) and hypoxia-inducible factor-1α (HIF-1α) were analyzed by Western blot in IFN-γ and TNF-α-treated Caco-2 monolayers. It was found that YC-1 attenuated barrier dysfunction caused by IFN-γ and TNF-α, and also prevented IFN-γ and TNF-α-induced morphological redistribution of tight junction proteins ZO-1 and occludin in Caco-2 monolayers. In addition, YC-1 suppressed IFN-γ and TNF-α-induced upregulation of MLC phosphorylation and MLCK protein expression. Furthermore, enhanced expression of HIF-1α in Caco-2 monolayers treated with IFN-γ and TNF-α was also suppressed by YC-1. It is suggested that YC-1, by downregulating MLCK expression, attenuates intestinal barrier dysfunction induced by IFN-γ and TNF-α, in which HIF-1α inhibition, at least in part, might by involved. YC-1 may be a potential agent for treatment of intestinal barrier disruption in inflammation.

Authors+Show Affiliations

State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21890376

Citation

Liu, Hang, et al. "Blockade of Hypoxia-inducible Factor-1α By YC-1 Attenuates Interferon-γ and Tumor Necrosis Factor-α-induced Intestinal Epithelial Barrier Dysfunction." Cytokine, vol. 56, no. 3, 2011, pp. 581-8.
Liu H, Li M, Wang P, et al. Blockade of hypoxia-inducible factor-1α by YC-1 attenuates interferon-γ and tumor necrosis factor-α-induced intestinal epithelial barrier dysfunction. Cytokine. 2011;56(3):581-8.
Liu, H., Li, M., Wang, P., & Wang, F. (2011). Blockade of hypoxia-inducible factor-1α by YC-1 attenuates interferon-γ and tumor necrosis factor-α-induced intestinal epithelial barrier dysfunction. Cytokine, 56(3), 581-8. https://doi.org/10.1016/j.cyto.2011.08.023
Liu H, et al. Blockade of Hypoxia-inducible Factor-1α By YC-1 Attenuates Interferon-γ and Tumor Necrosis Factor-α-induced Intestinal Epithelial Barrier Dysfunction. Cytokine. 2011;56(3):581-8. PubMed PMID: 21890376.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blockade of hypoxia-inducible factor-1α by YC-1 attenuates interferon-γ and tumor necrosis factor-α-induced intestinal epithelial barrier dysfunction. AU - Liu,Hang, AU - Li,Mu, AU - Wang,Pei, AU - Wang,Fengjun, Y1 - 2011/09/03/ PY - 2011/05/17/received PY - 2011/07/07/revised PY - 2011/08/05/accepted PY - 2011/9/6/entrez PY - 2011/9/6/pubmed PY - 2012/3/16/medline SP - 581 EP - 8 JF - Cytokine JO - Cytokine VL - 56 IS - 3 N2 - Proinflammatory cytokines play vital roles in intestinal barrier function disruption. YC-1 has been reported to have potent anti-inflammatory properties, and to be a potential agent for sepsis treatment. Here, we investigated the protective effect of YC-1 against intestinal barrier dysfunction caused by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). To assess the protective effect of YC-1 on intestinal barrier function, Caco-2 monolayers treated with simultaneous IFN-γ and TNF-α were used to measure transepithelial electrical resistance (TER) and paracellular permeability. To determine the mechanisms involved in the protective action of YC-1, expression and distribution of tight junction proteins ZO-1 and occludin in Caco-2 monolayers challenged with simultaneous IFN-γ and TNF-α were analyzed by Western blot and immunofluorescence, respectively. Expressions of phosphorylated myosin light chain (MLC), MLC kinase (MLCK) and hypoxia-inducible factor-1α (HIF-1α) were analyzed by Western blot in IFN-γ and TNF-α-treated Caco-2 monolayers. It was found that YC-1 attenuated barrier dysfunction caused by IFN-γ and TNF-α, and also prevented IFN-γ and TNF-α-induced morphological redistribution of tight junction proteins ZO-1 and occludin in Caco-2 monolayers. In addition, YC-1 suppressed IFN-γ and TNF-α-induced upregulation of MLC phosphorylation and MLCK protein expression. Furthermore, enhanced expression of HIF-1α in Caco-2 monolayers treated with IFN-γ and TNF-α was also suppressed by YC-1. It is suggested that YC-1, by downregulating MLCK expression, attenuates intestinal barrier dysfunction induced by IFN-γ and TNF-α, in which HIF-1α inhibition, at least in part, might by involved. YC-1 may be a potential agent for treatment of intestinal barrier disruption in inflammation. SN - 1096-0023 UR - https://www.unboundmedicine.com/medline/citation/21890376/Blockade_of_hypoxia_inducible_factor_1��_by_YC_1_attenuates_interferon_��_and_tumor_necrosis_factor_��_induced_intestinal_epithelial_barrier_dysfunction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-4666(11)00686-7 DB - PRIME DP - Unbound Medicine ER -