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Article

Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced inflammasome activation in human gingival epithelial cells

  • Authors:
    • Hong Li
    • Xiaoli Zhou
    • Jianli Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Stomatology, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China
  • Pages: 1039-1044
    |
    Published online on: July 25, 2014
       https://doi.org/10.3892/ijmm.2014.1865
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Abstract

Interleukin-1β (IL-1β) is a pathogenic factor for the destruction of periodontal tissue in periodontitis. The processing of IL-1β is regulated by cytosolic machinery termed as the inflammasome, which recruits and activates caspase-1 and then cleaves pro-IL-1β to produce mature IL-1β. Porphyromonas gingivalis (P. gingivalis) infection and lipopolysaccharide (LPS) have been shown to activate the NLRP3 inflammasome and stimulate IL-1β production in human oral cells. Heme oxygenase-1 (HO-1) is an ubiquitous cytoprotective enzyme. The products of HO-1 exhibit protective biological activities, including antioxidant and anti-inflammatory effects. In the present study, we investigated the hypothesis that the induction of HO-1 inhibits the activation of the inflammasome and protects against LPS-induced inflammatory damage in cultured human gingival epithelial cells (GECs). Our results revealed that LPS induced the overexpression of the inflammasome components, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1, by western blot analysis. Co-immunoprecipitation analysis indicated that LPS increased the binding of NLRP3 and ASC, and confocal imaging revealed that LPS increased the immunostaining and co-localization of ASC and caspase-1, indicating that LPS enhanced the assembly/formation of the inflammasome components. Hemin, a potent HO-1 inducer, blocked the LPS-induced overexpression and the formation of the NLRP3 inflammasome. Furthermore, hemin also inhibited the LPS-induced increase in the production of IL-1β, as shown by enzyme-linked immunosorbent assay and blocked the nuclear translocation of pro-inflammatory nuclear factor-κB (NF-κB), as shown by confocal assays. As a result, hemin protected the cells from LPS-induced damage, which was demonstrated by the immunostaining pattern of the cell junction protein, E-cadherin. LPS produced a disturbed staining pattern of E-cadherin, suggesting the disruption of epithelial integrity, which was abolished in the hemin-treated cells. In conclusion, our data demonstrate that the induction of HO-1 by hemin attenuates LPS-induced inflammatory damage in human GECs through the inhibition of inflammasome activation.
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Copy and paste a formatted citation
Spandidos Publications style
Li H, Zhou X and Zhang J: Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced inflammasome activation in human gingival epithelial cells. Int J Mol Med 34: 1039-1044, 2014.
APA
Li, H., Zhou, X., & Zhang, J. (2014). Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced inflammasome activation in human gingival epithelial cells. International Journal of Molecular Medicine, 34, 1039-1044. https://doi.org/10.3892/ijmm.2014.1865
MLA
Li, H., Zhou, X., Zhang, J."Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced inflammasome activation in human gingival epithelial cells". International Journal of Molecular Medicine 34.4 (2014): 1039-1044.
Chicago
Li, H., Zhou, X., Zhang, J."Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced inflammasome activation in human gingival epithelial cells". International Journal of Molecular Medicine 34, no. 4 (2014): 1039-1044. https://doi.org/10.3892/ijmm.2014.1865
Copy and paste a formatted citation
x
Spandidos Publications style
Li H, Zhou X and Zhang J: Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced inflammasome activation in human gingival epithelial cells. Int J Mol Med 34: 1039-1044, 2014.
APA
Li, H., Zhou, X., & Zhang, J. (2014). Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced inflammasome activation in human gingival epithelial cells. International Journal of Molecular Medicine, 34, 1039-1044. https://doi.org/10.3892/ijmm.2014.1865
MLA
Li, H., Zhou, X., Zhang, J."Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced inflammasome activation in human gingival epithelial cells". International Journal of Molecular Medicine 34.4 (2014): 1039-1044.
Chicago
Li, H., Zhou, X., Zhang, J."Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced inflammasome activation in human gingival epithelial cells". International Journal of Molecular Medicine 34, no. 4 (2014): 1039-1044. https://doi.org/10.3892/ijmm.2014.1865
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