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  Nitration of Wheat Amylase Trypsin Inhibitors Increases Their Innate and Adaptive Immunostimulatory Potential in vitro

Ziegler, K., Neumann, J., Liu, F., Fröhlich-Nowoisky, J., Cremer, C., Saloga, J., et al. (2019). Nitration of Wheat Amylase Trypsin Inhibitors Increases Their Innate and Adaptive Immunostimulatory Potential in vitro. Frontiers in immunology, 9: 3174. doi:10.3389/fimmu.2018.03174.

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 Creators:
Ziegler, Kira1, Author              
Neumann, Jan1, Author              
Liu, Fobang1, Author              
Fröhlich-Nowoisky, Janine2, Author              
Cremer, Christoph1, Author              
Saloga, Joachim3, Author
Reinmuth-Selzle, Kathrin1, Author              
Pöschl, Ulrich1, Author              
Schuppan, Detlef3, Author
Bellinghausen, Iris3, Author
Lucas, Kurt1, Author              
Affiliations:
1Multiphase Chemistry, Max Planck Institute for Chemistry, Max Planck Society, ou_1826290              
2Biogeochemistry, Max Planck Institute for Chemistry, Max Planck Society, ou_1826286              
3external, ou_persistent22              

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 Abstract: Amylase trypsin inhibitors (ATI) can be found in all gluten containing cereals and are, therefore, ingredient of basic foods like bread or pasta. In the gut ATI can mediate innate immunity via activation of the Toll-like receptor 4 (TLR4) on immune cells residing in the lamina propria, promoting intestinal, as well as extra-intestinal, inflammation. Inflammatory conditions can induce formation of peroxynitrite (ONOO−) and, thereby, endogenous protein nitration in the body. Moreover, air pollutants like ozone (O3) and nitrogen dioxide (NO2) can cause exogenous protein nitration in the environment. Both reaction pathways may lead to the nitration of ATI. To investigate if and how nitration modulates the immunostimulatory properties of ATI, they were chemically modified by three different methods simulating endogenous and exogenous protein nitration and tested in vitro. Here we show that ATI nitration was achieved by all three methods and lead to increased immune reactions. We found that ATI nitrated by tetranitromethane (TNM) or ONOO− lead to a significantly enhanced TLR4 activation. Furthermore, in human primary immune cells, TNM nitrated ATI induced a significantly higher T cell proliferation and release of Th1 and Th2 cytokines compared to unmodified ATI. Our findings implicate a causative chain between nitration, enhanced TLR4 stimulation, and adaptive immune responses, providing major implications for public health, as nitrated ATI may strongly promote inhalative wheat allergies (baker's asthma), non-celiac wheat sensitivity (NCWS), other allergies, and autoimmune diseases. This underlines the importance of future work analyzing the relationship between endo- and exogenous protein nitration, and the rise in incidence of ATI-related and other food hypersensitivities.

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Language(s): eng - English
 Dates: 2019
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000456183100001
DOI: 10.3389/fimmu.2018.03174
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Title: Frontiers in immunology
  Abbreviation : Front immunol
Source Genre: Journal
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Publ. Info: Lausanne : Frontiers Media
Pages: - Volume / Issue: 9 Sequence Number: 3174 Start / End Page: - Identifier: ISSN: 1664-3224
CoNE: https://pure.mpg.de/cone/journals/resource/1664-3224