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The following 2 abstracts suggest that free radical production promoted by
gliadin may be involved in the process of gluten-intolerance. Even in
NORMAL blood serum, gliadin promotes IgE, IgG and free radicals. Could
these free radicals be the trigger of celiac disease (CD)? Could
antioxidant therapy or supplementation prevent CD from being triggered in
individuals not yet showing CD symptoms? Can antioxidants reduce CD
symptoms and prevent other food allergies from occuring in CD patients?
These are intriguing questions, and neither medical science nor I have the
answers at this time.
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Cytokine. 2003 Mar 21;21(6):270-80.
Wheat gliadin promotes the interleukin-4-induced IgE production by normal
human peripheral mononuclear cells through a redox-dependent mechanism.
Dugas B, Dugas N, Conti M, Calenda A, Pino P, Thomas Y, Mazier D,
Vouldoukis I.
Isocell Nutra SAS, 53 bd du General Martial Valion, 75015 Paris, France.
[log in to unmask]
Increased levels of serum IgE have been described in gliadin-intolerant
patients; however, biological mechanisms implicated in this immunoglobulin
production remained unknown. In this study, we demonstrated that in vitro
crude gliadins and gliadin lysates (Glilys) promoted the IL-4-induced IgE
production by human peripheral blood mononuclear cells (PBMC), indicating
that the biological process related to gliadin intolerance and/or allergy
may lead to IgE production in vivo. It was found that crude gliadin and
Glilys potentiated, after 13 days of culture in a dose-dependent manner, IL-
4-induced IgE production and, to a lesser extent, the IgG production, while
they did not affect IgA or IgM productions. This promoting effect of
gliadin and Glilys on the IL-4-induced activation of normal human PBMC was
also observed on the early release (2 days) of the soluble fraction of
CD23, suggesting its possible involvement in IgE potentiation. The
promoting effect of crude gliadin and Glilys appeared to be indirect
because they did not modify purified B-lymphocytes IgE production after IL-
4 and anti-CD40 monoclonal antibody stimulation.In addition, as revealed by
luminol-dependent chemiluminescence, we demonstrated that crude gliadin and
Glilys promoted a substantial production of free radicals by normal human
PBMC, treated or not with IL-4. This redox imbalance associated with an
increased IgE production led us to evaluate the effect of pharmacological
antioxidants (N-acetyl-cysteine (NAC) and Cu/Zn-superoxide dismutase
(SOD1)) on IgE production by human PBMC. The NAC and the intracellularly
delivered SOD1 were found to suppress the IL-4+/-crude gliadin or Glilys-
induced IgE production by normal human PBMC. Taken together, these data
indicated that gliadin specifically enhanced IL-4-induced IgE production by
normal human PBMC, probably by the regulation of redox pathways, and that
this 'pro-allergenic' effect could be counteracted by natural antioxidants:
thiols and/or vectorized SOD1.
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Biochim Biophys Acta. 1999 Jan 6;1453(1):152-60.
In vitro cytotoxic effect of wheat gliadin-derived peptides on the Caco-2
intestinal cell line is associated with intracellular oxidative imbalance:
implications for coeliac disease.
Rivabene R, Mancini E, De Vincenzi M.
Laboratory of Metabolism and Pathological Biochemistry, Istituto Superiore
di Sanita, Rome, Italy. [log in to unmask]
Coeliac disease (CD) is an inflammatory disorder of the upper small
intestine in which gluten acts as an essential factor in its pathogenesis.
Although it is generally accepted that cereal protein activation of the
immune system is involved in CD progression, a non-immunomediated cytotoxic
activity of gliadin-derived peptides on the jejunal/duodenal tract cannot
be excluded. In this work, considering that (a) little has been reported
about the intracellular metabolic events associated with gliadin toxicity,
and (b) an important role for free radicals in a number of gastrointestinal
disease has been demonstrated, we investigated the in vitro effects of
gliadin-derived peptides on redox metabolism of Caco-2 intestinal cells
during a kinetic study in which cells were exposed to peptic-tryptic digest
of bread wheat up to 48 h. We found that the antiproliferative effects
displayed by gliadin exposure was associated with intracellular oxidative
imbalance, characterised by an increased presence of lipid peroxides, an
augmented oxidised (GSSG)/reduced (GSH) glutathione ratio and a loss in
protein-bound sulfhydryl groups. Significant structural perturbations of
the cell plasma membrane were also detected. Additional experiments
performed by using the specific GSH-depleting agent buthionine sulfoximine
provide evidence that the extent of gliadin-induced cell growth arrest
critically depends upon the 'basal' redox profile of the enterocytes. On
the whole, these findings seem to suggest that, besides the adoption of a
strictly gluten-free diet, the possibility for an adjuvant therapy with
antioxidants may be considered for CD patients.
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