Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
Animal Nutrition Group, Wageningen University, Wageningen, the Netherlands.
J Adv Res. 2022 Jul;39:305-318. doi: 10.1016/j.jare.2021.10.013. Epub 2021 Nov 1.
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.
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.
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.
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.
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.
肺炎缺乏有效的抗炎疗法，这是寻找新替代方法的挑战。由于非消化性半乳糖寡糖（GOS）具有局部和全身的抗炎和免疫调节作用，因此它们是有吸引力的候选物。
本研究旨在研究 GOS 对患有肺部感染的小牛以及小牛原代支气管上皮细胞（PBEC）和人肺上皮细胞（A549）的抗炎特性。为了阐明其机制，研究了 GOS 抑制 NOD 样受体家族含pyrin 结构域 3（NLRP3）炎性体的潜在能力。
在生命早期，将 GOS 口服给予患有自然发生肺部感染的小牛，或在暴露于溶血嗜血杆菌、脂多糖（LPS）、白细胞毒素或 ATP 的细胞培养物中用作预处理。研究支气管肺泡灌洗液（BALF）和血液中的细胞成分、细胞因子/趋化因子浓度以及溶血嗜血杆菌-LPS IgG 水平，同时检测体内 BALF 和支气管黏膜中的溶血嗜血杆菌阳性率。在体内和体外测量 NLRP3 炎性体激活的关键标志物。
GOS 降低了患有肺部感染的小牛中的溶血嗜血杆菌阳性率和溶血嗜血杆菌-LPS IgG 水平。GOS 调节免疫功能和抑制炎症反应与 NLRP3 炎性体的抑制有关，这在感染小牛的支气管黏膜组织中得到了观察。GOS 降低了溶血嗜血杆菌诱导的 PBEC 中 IL-1β 的产生，这与活性氧和 ATP 产生减少引起的 NLRP3 炎性体抑制有关。GOS 抑制了 PBEC 中的白细胞毒素诱导的 ATP 产生。GOS 抑制了 LPS 和 ATP 诱导的 PBEC 和 A549 细胞中的 NLRP3 炎性体激活。
GOS 通过体外和体内抑制 NLRP3 炎性体的激活发挥抗炎作用，这表明 GOS 在预防肺部感染方面具有潜在作用。
