Patulin influences the expression of Th1/Th2 cytokines

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Patulin influences the expression of Th1/Th2 cytokines by activated peripheral

blood mononuclear cells and T cells through depletion of intracellular

glutathione

Petra Luft1, Gertie Janneke Oostingh1, Gruijthuijsen1, Jutta

Horejs-Hoeck1, Irina Lehmann2, Albert Duschl1,*Article first published online:

23 JAN 2008

Keywords:patulin;cytokines;Th1/Th2;glutathione

Abstract

Patulin is a mold toxin secreted mainly by fungi of the Penicillium species.

Exposure generally results from consumption of moldy fruits and fruit products.

Since recent studies identified mold exposure as a risk factor for allergic

diseases, we examined the effects of patulin on human peripheral blood

mononuclear cells (PBMC) prepared from buffy coats of healthy donors. Cells were

stimulated with CD3- and CD28-specific antibodies in the presence or absence of

patulin. Effects of patulin on PBMCs were evaluated by proliferation, viability

assays, and cytokine ELISAs. The presence of 50 ng/mL patulin strongly decreased

the amounts of several cytokines in the supernatant of stimulated PBMCs. This

decrease in cytokine secretion was not due to cytotoxic effects of patulin.

Moreover, the extent of the reduction of cytokine amounts was cytokine specific,

affecting some (IL-4, IL-13, IFN, and IL-10), but not others (IL-8, IL-5). We

show that all effects could be abolished by adding thiol containing compounds. A

depletion of intracellular GSH could be measured after incubation of cells with

patulin. Taken together, our data indicate that patulin modulates the functional

activation of PBMCs with respect to proliferation and cytokine secretion

patterns by depletion of intracellular GSH. The depletion of intracellular

glutathione may influence the balance between Th1 and Th2 cells and have

implications for allergic diseases. © 2008 Wiley Periodicals, Inc. Environ

Toxicol, 2008.

http://onlinelibrary.wiley.com/doi/10.1002/tox.20309/abstract

PDF

http://onlinelibrary.wiley.com/doi/10.1002/tox.20309/pdf

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Mycotoxin-induced depletion of intracellular glutathione and altered cytokine

production in the human alveolar epithelial cell line A549

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Exposure to Mycotoxins Increases the Allergic Immune Response in a Murine Asthma

Model

Schütze1,2, Irina Lehmann1, Ulrike Bönisch1,2, Jan C. Simon2 and Tobias

Polte1,2

1 UFZ – Helmholtz Centre for Environmental Research Leipzig-Halle, Department of

Environmental Immunology, Leipzig, Germany; and 2 Department of Dermatology,

Venereology, and Allergology, Leipzig University Medical Center, Leipzig,

Germany

Correspondence and requests for reprints should be addressed to Tobias Polte,

Ph.D., UFZ – Helmholtz Centre for Environmental Research Leipzig-Halle,

Helmholtz University Young Investigators Group LIPAD. Department of

Environmental Immunology, Permoserstr. 15, 04318 Leipzig, Germany. E-mail:

tobias.polte@...

Rationale: Epidemiological studies have shown that indoor molds are associated

with increased prevalence and exacerbation of respiratory symptoms and asthma.

Mycotoxins, secondary metabolites of molds, may contribute to these effects.

Objectives: To investigate the adjuvant activity of mycotoxins on allergic

airway inflammation.

Methods: Balb/c mice were exposed via the airways to gliotoxin and via the

intestine to patulin, sensitized with ovalbumin (OVA), and then analyzed in

acute and chronic murine asthma models. In addition, the effect of mycotoxin

exposure on dendritic cell (DC) function was investigated using murine bone

marrow–derived DCs.

Measurements and Main Results: Exposure of mice to both mycotoxins enhanced

dose-dependently airway hyperreactivity, eosinophilic lung inflammation, and

OVA-specific IgE serum levels compared with mice that received only the antigen.

These findings correlated with increased Th2 cytokine levels and decreased IFN-

production. Long-term mycotoxin exposure exacerbated chronic airway inflammation

and airway remodeling. In vitro or in vivo mycotoxin exposure inhibited IL-12

production in maturing DCs and enhanced airway inflammation after adoptive DC

transfer into Balb/c mice. Mycotoxin exposure enhanced OVA-induced lung lipid

peroxidation and moderately increased isoprostane levels in naive mice.

Treatment of mycotoxin-exposed DCs with the antioxidants N-acetylcysteine or

glutathione ethyl ester restored IL-12 secretion and pretreatment of exposed

mice with N-acetylcysteine prevented the mycotoxin-induced increase of airway

inflammation and AHR.

Conclusions: Our results demonstrate that gliotoxin and patulin increase the

allergic immune response in mice by modulating the Th1/Th2 balance via direct

effects on IL-12 secretion in DCs and by inducing oxidative stress.

Key Words: air pollution • allergy • dendritic cells • Th1/Th2 cells

AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject

Exposure to indoor molds is associated with increased prevalence and

exacerbation of respiratory symptoms and asthma.

What This Study Adds to the field

Our results demonstrate that mycotoxins, secondary metabolites of molds, may be

responsible for these effects by interfering with dendritic cell function

leading to decreased Th1 differentiation and by inducing oxidative stress in the

lung.

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