Galacto-oligosaccharides alleviate lung inflammation by inhibiting NLRP3 inflammasome activation in vivo and in vitro.

Autor:	Cai Y; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, the Netherlands., Gilbert MS; Animal Nutrition Group, Wageningen University, Wageningen, the Netherlands., Gerrits WJJ; Animal Nutrition Group, Wageningen University, Wageningen, the Netherlands., Folkerts G; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, the Netherlands., Braber S; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, the Netherlands. Electronic address: S.Braber@uu.nl.
Jazyk:	angličtina
Zdroj:	Journal of advanced research [J Adv Res] 2022 Jul; Vol. 39, pp. 305-318. Date of Electronic Publication: 2021 Nov 01.
DOI:	10.1016/j.jare.2021.10.013
Abstrakt:	Introduction: The lack of effective anti-inflammatory therapies for pneumonia represents a challenge for identifying new alternatives. Non-digestible galacto-oligosaccharides (GOS) are attractive candidates due to their anti-inflammatory and immunomodulatory effects both locally and systemically. Objectives: The anti-inflammatory properties of GOS were investigated in calves with lung infections and in calf primary bronchial epithelial cells (PBECs) and human lung epithelial cells (A549). To delineate the mechanism, the potential capacity of GOS to inhibit the NLR family pyrin domain containing 3 (NLRP3) inflammasome has been investigated. Methods: GOS were administrated orally to calves with naturally occurring lung infections during early life or used as pretreatments in cell cultures exposed to M. haemolytica, lipopolysaccharides (LPS), leukotoxin or ATP. The cell composition, cytokine/chemokine concentrations, and M. haemolytica-LPS lgG levels in broncho-alveolar lavage fluid (BALF) and blood were investigated, while the M. haemolytica positivity in BALF and bronchial mucosa was detected in vivo. Key markers of NLRP3 inflammasome activation were measured in vivo and in vitro. Results: GOS reduced M. haemolytica positivity and M. haemolytica-LPS lgG levels in calves with lung infections. Regulation of immune function and suppression of inflammatory response by GOS is related to the inhibition of NLRP3 inflammasome as observed in bronchial mucosal tissue of infected calves. The M. haemolytica-induced IL-1β production in PBECs was lowered by GOS, which was associated with NLRP3 inflammasome inhibition caused by the decreased reactive oxygen species and ATP production. GOS inhibited leukotoxin-induced ATP production in PBECs. The LPS- and ATP-induced NLRP3 inflammasome activation in PBECs and A549 cells was suppressed by GOS. Conclusion: GOS exert anti-inflammatory properties by inhibiting the NLRP3 inflammasome activation in vitro and in vivo, suggesting a potential role for GOS in the prevention of lung infections. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022. Production and hosting by Elsevier B.V.)
Databáze:	MEDLINE
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