Human lactoferrin attenuates the proinflammatory response of neonatal monocyte-derived macrophages.
Human lactoferrin attenuates the proinflammatory response of neonatal monocyte-derived macrophages.
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DOI：
10.1111/cei.13108
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发表时间：
2018-06
影响因子：
4.6
通讯作者：
Sadeghi K
中科院分区：
文献类型：
--
作者：
Wisgrill L;Wessely I;Spittler A;Förster-Waldl E;Berger A;Sadeghi K
母乳中的生物活性成分，如人乳铁蛋白（hLF），在肠道微生物群稳态和预防新生儿炎症性疾病中发挥重要作用。新生儿肠道巨噬细胞显示促炎特征，可能有助于炎症性粘膜损伤。因此，本研究的目的是研究hLF对单核细胞源性巨噬细胞（momφ）分化和激活的免疫调节作用。从足月新生儿的脐带血和健康成人的外周血中分离单核细胞，在缺乏或存在hLF的情况下进行分化，并对分化、凋亡和吞噬进行评估。在脂多糖（LPS）和脂质胆酸（LTA）刺激下，研究了细胞因子的产生、Toll样受体（TLR）信号传导和激活标志物的表达。研究表明，hLF分化的momφ表现出TLR‐4表达、TLR信号传导、促炎细胞因子分泌和细胞内肿瘤坏死因子（TNF）‐α产生的降低。分化标志物、形态学和诱导凋亡的研究显示，乳铁蛋白分化的momφ没有改变。综上所述，hLF通过TLR表达和通路干扰促进无能/抗炎作用，导致促炎momφ表型减弱。hLF的无能/抗炎特性可能有助于预防早产儿发育中的肠道中有害的TLR介导的炎症性疾病。
Bioactive components of human milk, such as human lactoferrin (hLF), play an essential role in gut microbiome homeostasis and protection against neonatal inflammatory diseases. Neonatal intestinal macrophages display a proinflammatory profile that might contribute to inflammatory mucosal injury. Therefore, the aim of the study was to investigate the immunomodulatory effects of hLF on differentiation and activation of monocyte‐derived macrophages (moMϕ). Monocytes isolated from umbilical cord blood of term neonates and peripheral blood of healthy adults were differentiated in the absence or presence of hLF, and differentiation, apoptosis and phagocytosis were evaluated. Cytokine production, Toll‐like receptor (TLR) signalling and activation marker expression were investigated upon activation with lipopolysaccharide (LPS) and lipoteichoic acid (LTA) challenge. We demonstrate that hLF‐differentiated moMϕ exhibit decreased TLR‐4 expression, TLR signalling, proinflammatory cytokine secretion and intracellular tumour necrosis factor (TNF)‐α production. Investigation of differentiation markers, morphology and induction of apoptosis showed no alteration in lactoferrin‐differentiated moMϕ. Taken together, hLF promote anergic/anti‐inflammatory effects by TLR expression and pathway interference, resulting in a diminished proinflammatory moMϕ phenotype. The anergic/anti‐inflammatory properties of hLF might contribute to the prevention of harmful TLR‐mediated inflammatory disorders in the developing gut of premature infants.
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影响因子：
4.9
作者：
van der Does, Anne M.;Bogaards, Sylvia J. P.;Nibbering, Peter H.
通讯作者：
Nibbering, Peter H.
影响因子：
3.6
作者：
Buccigrossi, Vittoria;De Marco, Giulio;Guarino, Alfredo
通讯作者：
Guarino, Alfredo
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.5
作者：
Fleetwood, Andrew J.;Dinh, Hang;Hamilton, John A.
通讯作者：
Hamilton, John A.
影响因子：
4.3
作者：
Curran, Colleen S.;Demick, Karen P.;Mansfield, John M.
通讯作者：
Mansfield, John M.