Mitigation of Gliadin-Induced Inflammation and Cellular Damage by Curcumin in Human Intestinal Cell Lines

Inflammation. 2021 Jun;44(3):873-889. doi: 10.1007/s10753-020-01383-x. Epub 2021 Jan 4.

Abstract

Wheat is a major diet from many years; apart from its nutritious value, the wheat protein gliadin is responsible for many inflammatory diseases like celiac disease (CD), and non-celiac gluten sensitivity (NCGS). In this study, the gliadin-induced inflammation and associated cellular damage along with the protective role of curcumin was evaluated using human intestinal cell lines (HCT-116 and HT-29) as a model. Cells were cultured and exposed to 160 μg/ml of gliadin, 100 μM H2O2, and 10 μM curcumin (3 h pretreatment) followed by the assessment of inflammation. Spectrophotometric methods, real-time-PCR, ELISA, Western blotting, and confocal microscopy techniques were used to assess inflammatory markers such as advanced oxidation protein products (AOPPs) level, activity of myeloperoxidase (MPO) and NADPH oxidase (NOX), cytokines, and cell damage markers. The results show that gliadin increases the AOPPs level and the activity of MPO and NOX expression. It enhances inflammation by increasing expression of pro-inflammatory cytokines, altered expression of anti-inflammatory, and regulatory cytokines. It exacerbates the cellular damage by increasing MMP-2 and 9 and decreasing integrin α and β expression. Gliadin promotes disease pathogenesis by inducing the inflammation and cellular damage which further alter the cellular homeostasis. The pretreatment of curcumin counteracts the adverse effect of gliadin and protect the cells via diminishing the inflammation and help the cell to regain the cellular morphology suggesting phytochemical-based remedial interventions against wheat allergies.

Keywords: celiac disease; cellular damage; curcumin; gliadin proteins; inflammation; qRT-PCR.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Celiac Disease / genetics
  • Celiac Disease / metabolism
  • Celiac Disease / pathology
  • Celiac Disease / prevention & control*
  • Curcumin / pharmacology*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Enteritis / genetics
  • Enteritis / metabolism
  • Enteritis / pathology
  • Enteritis / prevention & control*
  • Gliadin / toxicity*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Inflammation Mediators / metabolism*
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / metabolism
  • Integrin beta Chains / genetics
  • Integrin beta Chains / metabolism
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Oxidative Stress
  • Signal Transduction
  • Wheat Hypersensitivity / genetics
  • Wheat Hypersensitivity / metabolism
  • Wheat Hypersensitivity / pathology
  • Wheat Hypersensitivity / prevention & control*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Integrin alpha Chains
  • Integrin beta Chains
  • Gliadin
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Curcumin