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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
Deoxynivalenol-induced proinflammatory gene expression: mechanisms and pathological sequelae
1Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. Pestka@msu.edu
Toxins
|November 10, 2011
Summary
Deoxynivalenol (DON), a common mycotoxin in cereals, triggers innate immune responses and endoplasmic reticulum stress. Understanding these mechanisms is key to managing DON
Area of Science:
- Toxicology
- Immunology
- Food Safety
Background:
- Deoxynivalenol (DON) is a prevalent trichothecene mycotoxin found globally in cereal grains due to Fusarium fungal contamination.
- Human health risks associated with acute and chronic DON ingestion require further investigation to ensure food safety without compromising nutritional value.
- The innate immune system's modulation is a critical factor in DON's toxicity.
Purpose of the Study:
- To elucidate the mechanisms underlying deoxynivalenol's toxic effects, focusing on innate immune system activation.
- To investigate the role of mitogen-activated protein kinases (MAPKs) and endoplasmic reticulum (ER) stress in DON toxicity.
- To identify potential biomarkers for assessing human health effects of DON exposure.
Main Methods:
- Investigated DON-induced activation of MAPKs in macrophages and monocytes.
- Examined the involvement of ribosome-associated protein kinases and GRP78 chaperone-mediated ER stress.
- Evaluated pathological outcomes of acute and chronic DON exposure in vivo.
Main Results:
- DON induces MAPK activation and pro-inflammatory gene expression in mononuclear phagocytes.
- DON triggers ribotoxic stress response via constitutive protein kinase activation and ER stress.
- Chronic exposure leads to anorexia, impaired weight gain, growth hormone dysregulation, and aberrant IgA production; acute exposure causes gastroenteritis and emesis.
Conclusions:
- DON's ability to induce ribotoxic stress in mononuclear phagocytes significantly contributes to its acute and chronic toxicity.
- Understanding these pathways is crucial for risk assessment and management of DON in the human diet.
- The study highlights the potential for identifying biomarkers to assess DON's impact on human health in epidemiological studies.
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