IL-13 is a central mediator of chemical-induced airway hyperreactivity in mice

Devos, Fien; Pollaris, Lore; Cremer, Jonathan; Seys, Sven; Hoshino, Tomoaki; Ceuppens, Jan L.; Talavera, Karel; Nemery, Benoît; Hoet, Peter; Vanoirbeek, Jeroen

doi:10.1371/journal.pone.0180690

Cited by 12 publications

(6 citation statements)

References 42 publications

(60 reference statements)

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“…The increased expression of Th2 cytokines IL-4 and IL-5 by airway inflammatory cells observed in our animal model is in agreement with previous experimental and clinical studies, which shows that these cytokines contribute either directly or indirectly to promoting the differentiation, survival, and function of key allergic effector cells (33). The level of IL-13, the presumed central mediator of murine allergic airway inflammation was the same either by OVA sensitization or after rAsp t 36-challenges (34,35). Conversely, IFN-γ being a cytokine that is released due to Th1 responses did not show any significant change after allergen challenge compared to control.…”

Section: Discussionsupporting

confidence: 92%

Identification and biochemical characterization of Asp t 36, a new fungal allergen from Aspergillus terreus

Karmakar

Saha

Jana

et al. 2020

Journal of Biological Chemistry

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Aspergillus terreus is an allergenic fungus in addition to causing infections in both humans and plants. However, the allergens in this fungus are still unknown, limiting the development of diagnostic and therapeutic strategies. We used a proteomic approach to search for allergens, identifying sixteen allergens based on two-dimensional immunoblotting with A. terreus susceptible patient sera. We further characterized triosephosphate isomerase (Asp t 36), one of the dominant immunoglobulin E (IgE)-reactive proteins. The gene was cloned and expressed in E. coli. Phylogenetic analysis showed Asp t 36 to be highly conserved with close similarity to the triosephosphate isomerase protein sequence from Dermatophagoides farinae, an allergenic dust mite. We identified four immuno-dominant epitopes using synthetic peptides, and mapped them on a homology-based model of the tertiary structure of Asp t 36. Among these, two were found to create a continuous surface patch on the 3D structure, rendering it an IgE binding hotspot. Biophysical analysis indicated that Asp t 36 shows similar secondary structure content and temperature sensitivity with other reported triosephosphate isomerase allergens. In vivo studies using a murine model displayed that the recombinant Asp t 36 was able to stimulate airway inflammation, as demonstrated by an influx of eosinophils, goblet cell hyperplasia, elevated serum immunoglobulins and induction of Th2 cytokines. Collectively, our results reveal the immunogenic property of Asp t 36, a major allergen from A. terreus, and define a new fungal allergen more broadly. This allergen could serve as a potent candidate for investigating component resolved diagnosis and immunotherapy.

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Section: Discussionsupporting

confidence: 92%

Identification and biochemical characterization of Asp t 36, a new fungal allergen from Aspergillus terreus

Karmakar

Saha

Jana

et al. 2020

Journal of Biological Chemistry

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“…Epithelial alarmin (TSLP)-induced IL-13 pathway was observed to be among the significantly perturbed pathways that was ameliorated by EUK-134 administration. TSLP is mainly produced by epithelial cells in allergic disorders such as asthma and atopic dermatitis [ 7 , 8 , [61] , [62] , [63] ]. Association between TSLP and disease severity has been reported in asthmatics [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Oxidant-induced epithelial alarmin pathway mediates lung inflammation and functional decline following ultrafine carbon and ozone inhalation co-exposure

et al. 2021

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Environmental inhalation exposures are inherently mixed (gases and particles), yet regulations are still based on single toxicant exposures. While the impacts of individual components of environmental pollution have received substantial attention, the impact of inhalation co-exposures is poorly understood. Here, we mechanistically investigated pulmonary inflammation and lung function decline after inhalation co-exposure and individual exposures to ozone (O 3 ) and ultrafine carbon black (CB). Environmentally/occupationally relevant lung deposition levels in mice were achieved after inhalation of stable aerosols with similar aerodynamic and mass median distributions. X-ray photoemission spectroscopy detected increased surface oxygen contents on particles in co-exposure aerosols. Compared with individual exposures, co-exposure aerosols produced greater acellular and cellular oxidants detected by electron paramagnetic resonance (EPR) spectroscopy, and in vivo immune-spin trapping (IST), as well as synergistically increased lavage neutrophils, lavage proteins and inflammation related gene/protein expression. Co-exposure induced a significantly greater respiratory function decline compared to individual exposure. A synthetic catalase-superoxide dismutase mimetic (EUK-134) significantly blunted lung inflammation and respiratory function decline confirming the role of oxidant imbalance. We identified a significant induction of epithelial alarmin (thymic stromal lymphopoietin-TSLP)-dependent interleukin-13 pathway after co-exposure, associated with increased mucin and interferon gene expression. We provided evidence of interactive outcomes after air pollution constituent co-exposure and identified a key mechanistic pathway that can potentially explain epidemiological observation of lung function decline after an acute peak of air pollution. Developing and studying the co-exposure scenario in a standardized and controlled fashion will enable a better mechanistic understanding of how environmental exposures result in adverse outcomes.

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“…Although it has less effect on mucus hyperplasia and airway hyperresponsiveness, IL-13 regulates airway hyperresponsiveness, promotes mucus hyperplasia, and has an important effect on the occurrence and development of allergic asthma [42]. IL-4, which is involved in the regulation of B cells, together with IL-13, induces the conversion of IgG to IgE and also upregulates the expression of vascular cell adhesion factor-1 (VCAM-1) [43]. After the allergic asthma model was induced in T cell immunodeficiency mice (without IL-4 and IL-13) by OVA, AHR and inflammation were significantly attenuated, and serum IgE and IgG1 levels were also greatly reduced [44].…”

Section: Discussionmentioning

confidence: 99%

Bifidobacterium infantis Relieves Allergic Asthma in Mice by Regulating Th1/Th2

et al. 2020

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Background:Bifidobacteria are among the probiotics used in treating intestinal diseases and are rarely used for allergic asthma treatment. The present study investigated the mechanism of B. infantis in treating allergic asthma in mice. Material/Methods:A total of 40 male Balb/c mice were randomized into control, ovalbumin (OVA), montelukast (Mon), and B. infantis (B10) groups, and allergic asthma was induced in the OVA, Mon, and B10 groups. Airway reactivity was measured on day 29 by methacholine at various doses. The numbers of total cells and inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted by blood cell counter and Diff-Quik staining. Hematoxylin-eosin (HE) staining was performed to observe inflammatory cell infiltration in lung tissues. Total IgE and OVA-specific IgE in serum were measured by ELISA. Mucin 5AC expression was detected by Western blot to evaluate airway obstruction. The levels of Th1 (IFN-g, IL-2) and Th2 (IL-4, IL-5, IL-13) cytokines in BALF and tissues were detected by ELISA and qRT-PCR, respectively. Results:The mice in the OVA group had airway hyperreactivity, while the symptoms in the B10 group and Mon group were effectively relieved. B10 reduced the number of inflammatory cells in BALF as well as inflammatory cell infiltration in tissues. Moreover, the levels of total serum IgE, OVA-specific IgE, and Mucin 5AC were increased in the OVA group, but were reduced in the Mon group and B10 group. B. infantis increased the levels of Th1 cytokines and decreased those of Th2 cytokines. Conclusions:B. infantis can reduce the infiltration of inflammatory cells induced by OVA-specific antibodies in mice. B. infantis has therapeutic effects on allergic asthma by promoting Th1 and inhibiting Th2 immune responses.

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IL-13 is a central mediator of chemical-induced airway hyperreactivity in mice

Cited by 12 publications

References 42 publications

Identification and biochemical characterization of Asp t 36, a new fungal allergen from Aspergillus terreus

Identification and biochemical characterization of Asp t 36, a new fungal allergen from Aspergillus terreus

Oxidant-induced epithelial alarmin pathway mediates lung inflammation and functional decline following ultrafine carbon and ozone inhalation co-exposure

Bifidobacterium infantis Relieves Allergic Asthma in Mice by Regulating Th1/Th2

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