Arabinogalactan isolated from cowshed dust extract protects mice from allergic airway inflammation and sensitization

Peters, Marcus; Kauth, Marion; Scherner, O.; Gehlhar, Kirsten; Steffen, Imke; Wentker, Pia; Mutius, Erika von; Holst, Otto; Bufe, Albrecht

doi:10.1016/j.jaci.2010.05.011

Cited by 77 publications

(75 citation statements)

References 36 publications

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“…Galactose and mannose shared strong negative correlations with inflammatory cell counts ) and with inflammatory cytokines observed in the present study. Mannose possesses broad anti-inflammatory effects against LPS-induced lung injury , while the product of arabinose and galactose, arabinogalactan, exhibits protection against allergic asthma (Peters et al 2010).…”

Section: Antiinflammatorymentioning

confidence: 99%

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

et al. 2014

Metabolomics

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The anti-malarial drug artesunate possesses anti-inflammatory and anti-oxidative actions in experimental asthma, comparable to corticosteroid. We hypothesized that artesunate may modulate disease-relevant metabolic alterations in allergic asthma. To explore metabolic profile changes induced by artesunate in allergic airway inflammation, we analysed bronchoalveolar lavage fluid (BALF) and serum from naïve and ovalbumininduced asthma mice treated with artesunate, using both gas and liquid chromatography-mass spectrometry metabolomics. Pharmacokinetics analyses of serum and lung tissues revealed that artesunate is rapidly converted into the active metabolite dihydroartemisinin. Artesunate effectively suppressed BALF total and differential counts, and repressed BALF Th2 cytokines, IL-17, IL-12(p40), MCP-1 and G-CSF levels. Artesunate had no effects on both BALF and serum metabolome in naïve mice. Artesunate promoted restoration of BALF sterols (cholesterol, cholic acid and cortol), phosphatidylcholines and carbohydrates (arabinose, mannose and galactose) and of serum 18-oxocortisol, galactose, glucose and glucouronic acid in asthma. Artesunate prevented OVA-induced increases in pro-inflammatory metabolites from arginine-proline metabolic pathway, particularly BALF levels of urea and alanine and serum levels of urea, proline, valine and homoserine. Multiple statistical correlation analyses revealed association between altered BALF and serum metabolites and inflammatory cytokines. Dexamethasone failed to reduce Wanxing Eugene Ho and Yong-Jiang Xu have contributed equally to this work.Electronic supplementary material The online version of this article (doi:10.1007/s11306-014-0699-x) contains supplementary material, which is available to authorized users. Metabolomics (2015) 11:380-390 DOI 10.1007 urea level and caused widespread changes in metabolites irrelevant to asthma development. Here we report the first metabolome profile of artesunate treatment in experimental asthma. Artesunate restored specific metabolic perturbations in airway inflammation, which correlated well with its anti-inflammatory actions. Our metabolomics findings further strengthen the therapeutic value of using artesunate to treat allergic asthma.

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Section: Antiinflammatorymentioning

confidence: 99%

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

et al. 2014

Metabolomics

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“…The efficient production of AG would be one major factor for a possible medical use of AG. We have shown previously that AG from these two related plants that belong to the same family is structurally similar (14).…”

Section: Discussionmentioning

confidence: 88%

“…Recently, we showed that treatment of mice with AG isolated from CDE prevents allergic airway inflammation, hyperreactivity, and sensitization (14). The allergy-protective role of AG seems to be mediated by attenuating the Th2-inducing properties of DCs, as shown by sensitization of mice with allergen-pulsed AG-treated bone marrow-derived DCs.…”

Section: Discussionmentioning

confidence: 99%

“…The raw AG-containing solution was concentrated by using a 30-kDa filtration unit (Merck Millipore, Billerica, MA). AG concentration was determined by b-D-glucosyl Yariv radial diffusion gel as described previously (14). For precipitation of AG, an appropriate amount of Yariv's reagent was added to the raw AG-containing solution.…”

Section: Reagents and Absmentioning

confidence: 99%

“…One allergy-protective molecule that makes up 13% of CDE total mass was identified as arabinogalactan (AG) (14). It was shown in a mouse asthma model that AG isolated from Alopecurus pratensis can prevent allergic airway inflammation and sensitization.…”

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confidence: 99%

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Allergy-Protective Arabinogalactan Modulates Human Dendritic Cells via C-Type Lectins and Inhibition of NF-κB

Peters

Guidato

Peters

et al. 2016

The Journal of Immunology

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Arabinogalactan (AG) isolated from dust of a traditional farm prevents disease in murine models of allergy. However, it is unclear whether this polysaccharide has immune regulatory properties in humans. The aim of this study was to test the influence of AG on the immune-stimulating properties of human dendritic cells (DCs). Moreover, we sought to identify the receptor to which AG binds. AG was produced from plant callus tissue under sterile conditions to avoid the influence of pathogen-associated molecular patterns in subsequent experiments. The influence of AG on the human immune system was investigated by analyzing its impact on monocyte-derived DCs. To analyze whether the T cell stimulatory capacity of AG-stimulated DCs is altered, an MLR with naive Th cells was performed. We revealed that AG reduced T cell proliferation in a human MLR. In the search for a molecular mechanism, we found that AG binds to the immune modulatory receptors DC-specific ICAM-3–grabbing non integrin (DC-SIGN) and macrophage mannose receptor 1 (MMR-1). Stimulation of these receptors with AG simultaneously with TLR4 stimulation with LPS increased the expression of the E3 ubiquitin-protein ligase tripartite motif–containing protein 21 and decreased the phosphorylation of NF-κB p65 in DCs. This led to a reduced activation profile with reduced costimulatory molecules and proinflammatory cytokine production. Blocking of MMR-1 or DC-SIGN with neutralizing Abs partially inhibits this effect. We conclude that AG dampens the activation of human DCs by LPS via binding to DC-SIGN and MMR-1, leading to attenuated TLR signaling. This results in a reduced T cell activation capacity of DCs.

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Cell Wall Polysaccharides

et al. 2021

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Arabinogalactan isolated from cowshed dust extract protects mice from allergic airway inflammation and sensitization

Cited by 77 publications

References 36 publications

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

Allergy-Protective Arabinogalactan Modulates Human Dendritic Cells via C-Type Lectins and Inhibition of NF-κB

Cell Wall Polysaccharides

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