Phloretin, an Apple Polyphenol, Inhibits Pathogen-Induced Mucin Overproduction.
Phloretin, an Apple Polyphenol, Inhibits Pathogen-Induced Mucin Overproduction.
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DOI：
10.1002/mnfr.202000658
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发表时间：
2021-01
影响因子：
5.2
通讯作者：
Leikauf GD
中科院分区：
文献类型：
--
作者：
Birru RL;Bein K;Wells H;Bondarchuk N;Barchowsky A;Di YP;Leikauf GD
细菌感染诱导粘液过度产生，导致慢性呼吸道疾病的急性加重和肺功能下降。富含苹果的饮食可以保护肺部疾病的发展和进展。本研究检测了根皮素（一种苹果多酚）是否抑制与慢性呼吸道疾病相关的主要细菌诱导的粘液合成和分泌。分析FVB/NJ小鼠和NCI-H292上皮细胞中粘液组分粘蛋白5AC（MUC 5AC）的表达。不可分型的流感嗜血杆菌（NTHi）感染的小鼠产生了MUC 5AC mRNA的增加，而含有根皮素的饮食抑制了这种增加。在NCI-H292细胞中，NTHi、卡他莫拉菌、肺炎链球菌和铜绿假单胞菌增加MUC 5AC mRNA，根皮素抑制MUC 5AC mRNA。根皮素还减少NTHi诱导的MUC 5AC蛋白分泌。NTHi诱导的MUC 5AC增加需要toll样受体4（TLR 4）和NADH氧化酶4（N 0X 4）信号传导以及随后的表皮生长因子受体（EGFR）/促分裂原活化蛋白激酶（MAPK）途径的活化。根皮素抑制NTHi诱导的TLR 4/N 0X 4和EGFR/MAPK信号传导，从而防止MUC 5AC mRNA增加。EGFR活化也可由EGFR配体合成增加和随后的基质金属蛋白酶（MMP）的配体活化引起。在NCI-H292细胞中，NTHi增加EGFR配体和MMP 1和MMP 13的mRNA，根皮素抑制。总之，根皮素是预防细菌诱导的粘液过度产生的有希望的治疗候选物。
Bacterial infection induces mucus overproduction, contributing to acute exacerbations and lung function decline in chronic respiratory diseases. A diet enriched in apples may provide protection from pulmonary disease development and progression. This study examined whether phloretin, an apple polyphenol, inhibits mucus synthesis and secretion induced by the predominant bacteria associated with chronic respiratory diseases. The expression of the mucus constituent mucin 5AC (MUC5AC) in FVB/NJ mice and NCI-H292 epithelial cells was analyzed. Nontypeable Haemophilus influenzae (NTHi)-infected mice developed increased MUC5AC mRNA, which a diet containing phloretin inhibited. In NCI-H292 cells, NTHi, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa increased MUC5AC mRNA, which phloretin inhibited. Phloretin also diminished NTHi-induced MUC5AC protein secretion. NTHi-induced increased MUC5AC required toll-like receptor 4 (TLR4) and NADH oxidase 4 (NOX4) signaling and subsequent activation of the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) pathway. Phloretin inhibited NTHi-induced TLR4/NOX4 and EGFR/MAPK signaling, thereby preventing increased MUC5AC mRNA. EGFR activation can also result from increased EGFR ligand synthesis and subsequent ligand activation by matrix metalloproteinases (MMPs). In NCI-H292 cells, NTHi increased EGFR ligand and MMP1 and MMP13 mRNA, which phloretin inhibited. In summary, phloretin is a promising therapeutic candidate for preventing bacterial-induced mucus overproduction.
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DOI：
10.1183/13993003.02286-2016
发表时间：
2017-12
期刊：
The European respiratory journal
影响因子：
--
作者：
Garcia-Larsen V;Potts JF;Omenaas E;Heinrich J;Svanes C;Garcia-Aymerich J;Burney PG;Jarvis DL
通讯作者：
Jarvis DL
影响因子：
24.3
作者：
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通讯作者：
Johnston, S. L.
影响因子：
15.9
作者：
Elkington, Paul;Shiomi, Takayuki;Friedland, Jon S.
通讯作者：
Friedland, Jon S.
影响因子：
7.7
作者：
Behzad, Sahar;Sureda, Antoni;Nabavi, Seyed Mohammad
通讯作者：
Nabavi, Seyed Mohammad
影响因子：
3.7
作者：
Hassan F;Ren D;Zhang W;Gu XX
通讯作者：
Gu XX