التفاصيل البيبلوغرافية
| العنوان: |
A Polysaccharide Virulence Factor from Aspergillus fumigatus Elicits Anti-inflammatory Effects through Induction of Interleukin-1 Receptor Antagonist. |
| المؤلفون: |
Gresnigt, Mark S., Bozza, Silvia, Becker, Katharina L., Joosten, Leo A. B., Abdollahi-Roodsaz, Shahla, van der Berg, Wim B., Dinarello, Charles A., Netea, Mihai G., Fontaine, Thierry, De Luca, Antonella, Moretti, Silvia, Romani, Luigina, Latge, Jean-Paul, van de Veerdonk, Frank L. |
| المصدر: |
PLoS Pathogens; Mar2014, Vol. 10 Issue 3, p1-10, 10p |
| مصطلحات موضوعية: |
GALACTOSAMINE, GALACTANS, ASPERGILLUS fumigatus, ANTI-inflammatory agents, CYTOKINES, INTERLEUKIN-1 receptor antagonist protein, ASPERGILLOSIS |
| مستخلص: |
The galactosaminogalactan (GAG) is a cell wall component of Aspergillus fumigatus that has potent anti-inflammatory effects in mice. However, the mechanisms responsible for the anti-inflammatory property of GAG remain to be elucidated. In the present study we used in vitro PBMC stimulation assays to demonstrate, that GAG inhibits proinflammatory T-helper (Th)1 and Th17 cytokine production in human PBMCs by inducing Interleukin-1 receptor antagonist (IL-1Ra), a potent anti-inflammatory cytokine that blocks IL-1 signalling. GAG cannot suppress human T-helper cytokine production in the presence of neutralizing antibodies against IL-1Ra. In a mouse model of invasive aspergillosis, GAG induces IL-1Ra in vivo, and the increased susceptibility to invasive aspergillosis in the presence of GAG in wild type mice is not observed in mice deficient for IL-1Ra. Additionally, we demonstrate that the capacity of GAG to induce IL-1Ra could also be used for treatment of inflammatory diseases, as GAG was able to reduce severity of an experimental model of allergic aspergillosis, and in a murine DSS-induced colitis model. In the setting of invasive aspergillosis, GAG has a significant immunomodulatory function by inducing IL-1Ra and notably IL-1Ra knockout mice are completely protected to invasive pulmonary aspergillosis. This opens new treatment strategies that target IL-1Ra in the setting of acute invasive fungal infection. However, the observation that GAG can also protect mice from allergy and colitis makes GAG or a derivative structure of GAG a potential treatment compound for IL-1 driven inflammatory diseases. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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