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人乳影响 Caco-2 肠上皮细胞中 TLR4 的激活和 LPS 诱导的炎症细胞因子表达。

Human milk affects TLR4 activation and LPS-induced inflammatory cytokine expression in Caco-2 intestinal epithelial cells.

机构信息

Division of Pediatric Allergy and Immunology, Center for Food Allergy, Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Golisano Children's Hospital, 601 Elmwood Ave, Box 777, Rochester, NY, 14642, USA.

Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.

出版信息

Sci Rep. 2024 Jun 11;14(1):13448. doi: 10.1038/s41598-024-64000-z.

DOI:10.1038/s41598-024-64000-z
PMID:38862662
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11167050/
Abstract

Human milk (HM) components affect immune cell toll-like receptor 4 (TLR4) signaling. However, studies examining the immunomodulatory impacts of HM on TLR4 signaling in intestinal epithelial cells (IECs) are limited. This study utilized both a TLR4 reporter cell line and a Caco-2 IEC model to examine the effects of HM on lipopolysaccharide (LPS)-induced TLR4 activation and cytokine responses, respectively. Additionally, we performed fast protein liquid chromatography and mass spectrometry to identify a HM component that contributes to the effect of HM on LPS/TLR4 signaling. HM enhances LPS-induced TLR4 signaling as well as LPS-induced IEC gene expression of pro-inflammatory cytokines and negative regulators of NF-κB. Human serum albumin (HSA) present in HM contributes to these effects. HSA within HM synergizes with LPS to induce IEC gene expression of pro-inflammatory cytokines and negative regulators of NF-κB. Altogether, this study provides mechanistic evidence behind the immunomodulatory function of HM on IECs, which may contribute to an enhanced immune response in breast-fed neonates.

摘要

人乳（HM）成分会影响免疫细胞 Toll 样受体 4（TLR4）信号。然而，研究 HM 对肠道上皮细胞（IEC）中 TLR4 信号的免疫调节作用的研究有限。本研究分别使用 TLR4 报告细胞系和 Caco-2 IEC 模型，研究了 HM 对脂多糖（LPS）诱导的 TLR4 激活和细胞因子反应的影响。此外，我们还进行了快速蛋白质液相色谱和质谱分析，以鉴定出一种 HM 成分，该成分对 HM 对 LPS/TLR4 信号的影响有贡献。HM 增强了 LPS 诱导的 TLR4 信号以及 LPS 诱导的 IEC 促炎细胞因子和 NF-κB 负调节剂的基因表达。HM 中存在的人血清白蛋白（HSA）促成了这些作用。HM 中的 HSA 与 LPS 协同诱导 IEC 促炎细胞因子和 NF-κB 负调节剂的基因表达。总的来说，这项研究为 HM 对 IEC 的免疫调节功能提供了机制证据，这可能有助于母乳喂养的新生儿增强免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/11167050/d8f0d98c85ab/41598_2024_64000_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/11167050/2cc55e866f3a/41598_2024_64000_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/11167050/0c285f693d6d/41598_2024_64000_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/11167050/8de23c19167b/41598_2024_64000_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/11167050/d8f0d98c85ab/41598_2024_64000_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/11167050/2cc55e866f3a/41598_2024_64000_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/11167050/0c285f693d6d/41598_2024_64000_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/11167050/8de23c19167b/41598_2024_64000_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/11167050/d8f0d98c85ab/41598_2024_64000_Fig4_HTML.jpg

相似文献

[1]
Human milk affects TLR4 activation and LPS-induced inflammatory cytokine expression in Caco-2 intestinal epithelial cells.

Sci Rep. 2024-6-11

[2]
Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide.

J Immunol. 2001-8-1

[3]
Bcl10 mediates LPS-induced activation of NF-kappaB and IL-8 in human intestinal epithelial cells.

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[4]
The In Vitro Anti-Inflammatory Activities of Galangin and Quercetin towards the LPS-Injured Rat Intestinal Epithelial (IEC-6) Cells as Affected by Heat Treatment.

Molecules. 2021-12-10

[5]
Regulation of Toll-like receptor 4-associated MD-2 in intestinal epithelial cells: a comprehensive analysis.

Innate Immun. 2009-8-26

[6]
Loss of CFTR affects biliary epithelium innate immunity and causes TLR4-NF-κB-mediated inflammatory response in mice.

Gastroenterology. 2011-6-26

[7]
Loganin alleviates LPS-activated intestinal epithelial inflammation by regulating TLR4/NF-κB and JAK/STAT3 signaling pathways.

Kaohsiung J Med Sci. 2020-4

[8]
TLR4 and MD-2 expression is regulated by immune-mediated signals in human intestinal epithelial cells.

J Biol Chem. 2002-6-7

[9]
MicroRNA Bta-miR-24-3p Suppressed Galectin-9 Expression through TLR4/NF-ĸB Signaling Pathway in LPS-Stimulated Bovine Endometrial Epithelial Cells.

Cells. 2021-11-25

[10]
Bacterial lipopolysaccharide induces increased expression of toll-like receptor (TLR) 4 and downstream TLR signaling molecules in bovine mammary epithelial cells.

Vet Res. 2008

本文引用的文献

[1]
Biomarkers of Development of Immunity and Allergic Diseases in Farming and Non-farming Lifestyle Infants: Design, Methods and 1 Year Outcomes in the "Zooming in to Old Order Mennonites" Birth Cohort Study.

Front Pediatr. 2022-7-6

[2]
Traditional Farming Lifestyle in Old Older Mennonites Modulates Human Milk Composition.

Front Immunol. 2021

[3]
Human Breast Milk Enhances Intestinal Mucosal Barrier Function and Innate Immunity in a Healthy Pediatric Human Enteroid Model.

Front Cell Dev Biol. 2021-7-13

[4]
Infant gut microbiome is enriched with Bifidobacterium longum ssp. infantis in Old Order Mennonites with traditional farming lifestyle.

Allergy. 2021-11

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Like Cures Like: Pharmacological Activity of Anti-Inflammatory Lipopolysaccharides From Gut Microbiome.

Front Pharmacol. 2020-4-30

[6]
Immunologically Active Components in Human Milk and Development of Atopic Disease, With Emphasis on Food Allergy, in the Pediatric Population.

Front Pediatr. 2018-8-7

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Toll-Like Receptors Drive Specific Patterns of Tolerance and Training on Restimulation of Macrophages.

Front Immunol. 2018-5-14

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The Intestinal Epithelium: Central Coordinator of Mucosal Immunity.

Trends Immunol. 2018-4-30

[9]
Human Milk Components Modulate Toll-Like Receptor-Mediated Inflammation.

Adv Nutr. 2016-1-15

[10]
Toll-like receptor 2 activators modulate oral tolerance in mice.

Clin Exp Allergy. 2015-11

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