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

Yang Cai; Myrthe S. Gilbert; Walter J.J. Gerrits; Gert Folkerts; Saskia Braber

doi:10.1016/j.jare.2021.10.013

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

Yang Cai
, Myrthe S. Gilbert
, Walter J.J. Gerrits
, Gert Folkerts
, Saskia Braber^*

^*Corresponding author for this work

Wageningen University & Research

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	305-318
Number of pages	14
Journal	Journal of Advanced Research
Volume	39
Early online date	1 Nov 2021
DOIs	https://doi.org/10.1016/j.jare.2021.10.013
Publication status	Published - Jul 2022

Bibliographical note

Funding Information:
This research was performed in the public-private partnership 'CarboKinetics' coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl ). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V., Cooperatie AVEBE U.A., DSM Food Specialties B.V., FrieslandCampina Nederland B.V., Nutrition Sciences N.V., VanDrie Holding N.V. and Sensus B.V., and allowances of The Netherlands Organisation for Scientific Research (NWO).

Funding Information:
This work was funded by the Netherlands Organisation for Scientific Research (NWO), grant number: ALWCC.2015.4. Research grant funding (No.201608320245) was received from the China Scholarship Council.

Funding Information:
This research was performed in the public-private partnership 'CarboKinetics' coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V. Cooperatie AVEBE U.A. DSM Food Specialties B.V. FrieslandCampina Nederland B.V. Nutrition Sciences N.V. VanDrie Holding N.V. and Sensus B.V. and allowances of The Netherlands Organisation for Scientific Research (NWO). The authors especially thank the VanDrie Group, Mijdrecht, The Netherlands, for providing technical assistance and lung tissue from calves. The authors are grateful to Prof. Jos van Putten for giving free access to all the facilities of his laboratory and for providing the Mannheimia haemolytica strain. This work was funded by the Netherlands Organisation for Scientific Research (NWO), grant number: ALWCC.2015.4. Research grant funding (No.201608320245) was received from the China Scholarship Council. The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions.

Publisher Copyright:
© 2021

Funding

This research was performed in the public-private partnership 'CarboKinetics' coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl ). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V., Cooperatie AVEBE U.A., DSM Food Specialties B.V., FrieslandCampina Nederland B.V., Nutrition Sciences N.V., VanDrie Holding N.V. and Sensus B.V., and allowances of The Netherlands Organisation for Scientific Research (NWO). This work was funded by the Netherlands Organisation for Scientific Research (NWO), grant number: ALWCC.2015.4. Research grant funding (No.201608320245) was received from the China Scholarship Council. This research was performed in the public-private partnership 'CarboKinetics' coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V. Cooperatie AVEBE U.A. DSM Food Specialties B.V. FrieslandCampina Nederland B.V. Nutrition Sciences N.V. VanDrie Holding N.V. and Sensus B.V. and allowances of The Netherlands Organisation for Scientific Research (NWO). The authors especially thank the VanDrie Group, Mijdrecht, The Netherlands, for providing technical assistance and lung tissue from calves. The authors are grateful to Prof. Jos van Putten for giving free access to all the facilities of his laboratory and for providing the Mannheimia haemolytica strain. This work was funded by the Netherlands Organisation for Scientific Research (NWO), grant number: ALWCC.2015.4. Research grant funding (No.201608320245) was received from the China Scholarship Council. The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions.

Keywords

IL-1β
Mannheimia haemolytica
Non-digestible oligosaccharides
Primary bronchial epithelial cells
Reactive oxygen species
Respiratory infections

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1-s2.0-S2090123221002095-mainFinal published version, 2.94 MBLicence: CC BY

Cite this

@article{e131450f8d2148f3a239ed2acc38499e,

title = "Galacto-oligosaccharides alleviate lung inflammation by inhibiting NLRP3 inflammasome activation in vivo and in vitro",

abstract = "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.",

keywords = "IL-1β, Mannheimia haemolytica, Non-digestible oligosaccharides, Primary bronchial epithelial cells, Reactive oxygen species, Respiratory infections",

author = "Yang Cai and Gilbert, \{Myrthe S.\} and Gerrits, \{Walter J.J.\} and Gert Folkerts and Saskia Braber",

note = "Funding Information: This research was performed in the public-private partnership 'CarboKinetics' coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl ). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V., Cooperatie AVEBE U.A., DSM Food Specialties B.V., FrieslandCampina Nederland B.V., Nutrition Sciences N.V., VanDrie Holding N.V. and Sensus B.V., and allowances of The Netherlands Organisation for Scientific Research (NWO). Funding Information: This work was funded by the Netherlands Organisation for Scientific Research (NWO), grant number: ALWCC.2015.4. Research grant funding (No.201608320245) was received from the China Scholarship Council. Funding Information: This research was performed in the public-private partnership 'CarboKinetics' coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V. Cooperatie AVEBE U.A. DSM Food Specialties B.V. FrieslandCampina Nederland B.V. Nutrition Sciences N.V. VanDrie Holding N.V. and Sensus B.V. and allowances of The Netherlands Organisation for Scientific Research (NWO). The authors especially thank the VanDrie Group, Mijdrecht, The Netherlands, for providing technical assistance and lung tissue from calves. The authors are grateful to Prof. Jos van Putten for giving free access to all the facilities of his laboratory and for providing the Mannheimia haemolytica strain. This work was funded by the Netherlands Organisation for Scientific Research (NWO), grant number: ALWCC.2015.4. Research grant funding (No.201608320245) was received from the China Scholarship Council. The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions. Publisher Copyright: {\textcopyright} 2021",

year = "2022",

month = jul,

doi = "10.1016/j.jare.2021.10.013",

language = "English",

volume = "39",

pages = "305--318",

journal = "Journal of Advanced Research",

issn = "2090-1232",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Galacto-oligosaccharides alleviate lung inflammation by inhibiting NLRP3 inflammasome activation in vivo and in vitro

AU - Cai, Yang

AU - Gilbert, Myrthe S.

AU - Gerrits, Walter J.J.

AU - Folkerts, Gert

AU - Braber, Saskia

N1 - Funding Information: This research was performed in the public-private partnership 'CarboKinetics' coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl ). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V., Cooperatie AVEBE U.A., DSM Food Specialties B.V., FrieslandCampina Nederland B.V., Nutrition Sciences N.V., VanDrie Holding N.V. and Sensus B.V., and allowances of The Netherlands Organisation for Scientific Research (NWO). Funding Information: This work was funded by the Netherlands Organisation for Scientific Research (NWO), grant number: ALWCC.2015.4. Research grant funding (No.201608320245) was received from the China Scholarship Council. Funding Information: This research was performed in the public-private partnership 'CarboKinetics' coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V. Cooperatie AVEBE U.A. DSM Food Specialties B.V. FrieslandCampina Nederland B.V. Nutrition Sciences N.V. VanDrie Holding N.V. and Sensus B.V. and allowances of The Netherlands Organisation for Scientific Research (NWO). The authors especially thank the VanDrie Group, Mijdrecht, The Netherlands, for providing technical assistance and lung tissue from calves. The authors are grateful to Prof. Jos van Putten for giving free access to all the facilities of his laboratory and for providing the Mannheimia haemolytica strain. This work was funded by the Netherlands Organisation for Scientific Research (NWO), grant number: ALWCC.2015.4. Research grant funding (No.201608320245) was received from the China Scholarship Council. The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions. Publisher Copyright: © 2021

PY - 2022/7

Y1 - 2022/7

N2 - 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.

AB - 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.

KW - IL-1β

KW - Mannheimia haemolytica

KW - Non-digestible oligosaccharides

KW - Primary bronchial epithelial cells

KW - Reactive oxygen species

KW - Respiratory infections

UR - https://www.scopus.com/pages/publications/85118895174

U2 - 10.1016/j.jare.2021.10.013

DO - 10.1016/j.jare.2021.10.013

M3 - Article

AN - SCOPUS:85118895174

SN - 2090-1232

VL - 39

SP - 305

EP - 318

JO - Journal of Advanced Research

JF - Journal of Advanced Research

ER -

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

Abstract

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Keywords

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