Allergic sensitization is associated with inadequate antioxidant responses in mice and men

Utsch, L.; Folisi, Caterina; Akkerdaas, Jaap H.; Logiantara, A.; Pol, Marianne A. van de; Zee, J.S. van der; Krop, Esmeralda; Lutter, René; Ree, Ronald van; Rijt, Leonie S. van

doi:10.1111/all.12674

Cited by 15 publications

(20 citation statements)

References 43 publications

(55 reference statements)

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“…Sensitization to house dust mite (HDM) in mice was associated with an incapacity to upregulate Nrf2 and HO-1 upon induction of oxidative stress by mite proteases. In BALB/c mice, exposure to a HDM extract with trace levels of endotoxins (LT-HDM) was not sufficient to induce a Th2 immune response [32]. This is in accordance with several studies showing that TLR4 triggering by LPS is crucial for the initiation of allergen-specific Th2 responses IN BALB/c mice [74,75].…”

Section: Allergic Sensitization Is Associated With a Decreased Antsupporting

confidence: 67%

“…In our lab, we recently demonstrated that HDM proteases are responsible for the capacity of HDM allergens to induce oxidative stress. Partial inhibition of protease activity dramatically decreased the capacity of HDM to induce oxidative stress and the subsequent allergic inflammation in mice [32]. …”

Section: Protease Allergens Trigger Reactive Oxygen Species Producmentioning

confidence: 99%

“…The ROS production or oxidative stress was not investigated in this experiment. Using a similar approach, we showed that the HDM induced activation of DCs could be inhibited by adding a potent anti-oxidant scavenger N -acetyl- l -cysteine during the pulsing with HDM or by heating HDM to eliminate protease activity [32]. These experiments indicate that proteolytic activity induces ROS, which can result in DC activation.…”

Section: Protease Allergens Trigger Reactive Oxygen Species Producmentioning

confidence: 99%

“…We recently observed in our lab that susceptibility for sensitization was associated with an inadequate anti-oxidant response in human. Newly employed animal workers were followed for two years for the development of allergy to rodent urinary proteins [32]. Individuals who became de novo-sensitized to urinary proteins had higher serum levels of 4-HNE modified proteins and a lower expression of HO-1 at baseline before allergen exposure.…”

Section: Allergic Sensitization Is Associated With a Decreased Antmentioning

confidence: 99%

“…Intranasal exposure to LT-HDM induced much less maturation of airway DCs compared to a HDM extract containing high levels of endotoxin (HT-HDM) [32,77,78]. Remarkably, C3H/HeJ mice were capable to exert a full-blown allergic type 2 inflammation after intranasal exposure to LT-HDM, despite a low-immunogenic profile of airway DCs (low levels of co-stimulatory surface proteins CD40, CD80, and CD86 compared to HT-HDM).…”

Section: Allergic Sensitization Is Associated With a Decreased Antmentioning

confidence: 99%

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Oxidative Stress: Promoter of Allergic Sensitization to Protease Allergens?

Rijt

Utsch

Lutter

et al. 2017

IJMS

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Allergies arise from aberrant T helper type 2 responses to allergens. Several respiratory allergens possess proteolytic activity, which has been recognized to act as an adjuvant for the development of a Th2 response. Allergen source-derived proteases can activate the protease-activated receptor-2, have specific effects on immune cells by cleaving cell membrane-bound regulatory molecules, and can disrupt tight junctions. The protease activity can induce a non-allergen-specific inflammatory response in the airways, which will set the stage for an allergen-specific Th2 response. In this review, we will discuss the evidence for the induction of oxidative stress as an underlying mechanism in Th2 sensitization to proteolytic allergens. We will discuss recent data linking the proteolytic activity of an allergen to its potential to induce oxidative stress and how this can facilitate allergic sensitization. Based on experimental data, we propose that a less proficient anti-oxidant response to allergen-induced oxidative stress contributes to the susceptibility to allergic sensitization. Besides the effect of oxidative stress on the immune response, we will also discuss how oxidative stress can increase the immunogenicity of an allergen by chemical modification.

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Section: Allergic Sensitization Is Associated With a Decreased Antsupporting

confidence: 67%

Section: Protease Allergens Trigger Reactive Oxygen Species Producmentioning

confidence: 99%

Section: Protease Allergens Trigger Reactive Oxygen Species Producmentioning

confidence: 99%

Section: Allergic Sensitization Is Associated With a Decreased Antmentioning

confidence: 99%

Section: Allergic Sensitization Is Associated With a Decreased Antmentioning

confidence: 99%

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Oxidative Stress: Promoter of Allergic Sensitization to Protease Allergens?

Rijt

Utsch

Lutter

et al. 2017

IJMS

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Immunotoxicity of organophosphate flame retardants TPHP and TDCIPP on murine dendritic cells in vitro

et al. 2017

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Organophosphate flame retardants (PFRs) are commonly used as alternatives for the banned polybrominated diphenyl ethers (PBDEs) and are ubiquitously detected in indoor dust. PFRs can be potentially hazardous to respiratory health via the inhalation of house dust. Dendritic cells (DCs) are crucial in the immunological defense against pathogens in the airways. In respiratory allergy however, an aberrant immune response is induced against innocuous proteins, like house dust mite allergens. In this study, we examined whether exposure to PFRs Triphenylphosphate (TPHP) and Tris(1,3-dichloroisopropyl) phosphate (TDCIPP) affected activation/maturation of DCs at steady state and during exposure to house dust mite allergens (HDM). Bone marrow-derived dendritic cells (BMDCs) were exposed to a concentration range of each PFR (0.1-100 μM) with or without HDM in vitro to analyze the effect on the expression of major histocompatibility complex class II (MHCII), co-stimulatory molecules and cytokine production. Concentrations of TPHP and TDCIPP of ≥50 μM were cytotoxic to BMDCs. At these cytotoxic concentrations, TPHP exposure induced an activated phenotype in steady state DCs, while HDM exposed DCs acquired a tolerogenic phenotype. In contrast, TDCIPP exposure had no effect at steady state DCs but suppressed the expression of MHCII, costimulatory molecules, and the IL-6 production in HDM exposed DCs. The cytotoxic concentrations induced the anti-oxidant enzyme hemeoxigenase-1, which is a marker for oxidative stress. These results demonstrate that PFRs can be immunotoxic for DCs and suggest the necessity to evaluate the effects on the immune system on a cellular level during the risk assessment of these alternative flame retardants.

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A time-dependently regulated gene network reveals that Aspergillus protease affects mitochondrial metabolism and airway epithelial cell barrier function via mitochondrial oxidants

Kim

et al. 2022

Free Radical Biology and Medicine

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Allergic sensitization is associated with inadequate antioxidant responses in mice and men

Abstract: Our study indicates that oxidative stress condition before allergen exposure due to an inadequate antioxidant response may prime for allergic Th2 responses.

Cited by 15 publications

References 43 publications

Oxidative Stress: Promoter of Allergic Sensitization to Protease Allergens?

Oxidative Stress: Promoter of Allergic Sensitization to Protease Allergens?

Immunotoxicity of organophosphate flame retardants TPHP and TDCIPP on murine dendritic cells in vitro

A time-dependently regulated gene network reveals that Aspergillus protease affects mitochondrial metabolism and airway epithelial cell barrier function via mitochondrial oxidants

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