The Human Cathelicidin LL-37 Host Defense Peptide Upregulates Tight Junction-Related Proteins and Increases Human Epidermal Keratinocyte Barrier Function

Eosinophilic esophagitis (EoE) is an allergy-mediated disease that is accompanied by IL-13 overexpression and an impaired esophageal barrier. Filaggrin (FLG) and tight junction (TJ) proteins are considered to contribute to epithelial barrier function. However, their functional involvement in EoE has not been elucidated. Here, we aimed to determine the IL-13-mediated barrier dysfunction and expression of TJ-related proteins in EoE and to characterize interactions among TJ-related proteins involved in the barrier function of the esophageal epithelium. Biopsy specimens from EoE patients were analyzed. Primary human esophageal epithelial cells (HEECs) were cultured using an air-liquid interface (ALI) system. The permeability of TJs was assayed by biotinylation. Transepithelial electrical resistance (TEER) was measured after stimulation with IL-13 and after siRNA silencing of FLG expression. FLG and TJ genes and proteins were assessed by quantitative RT-PCR, Western blot analysis, and immunofluorescent staining. The biotinylation reagent diffused through the paracellular spaces of whole stratified epithelial layers in EoE biopsy samples. The TEER decreased in ALI-cultured HEECs after IL-13 stimulation. Although the protein level of FLG decreased, that of the TJ proteins increased in the mucosa of EoE biopsy samples and in ALI-cultured HEECs after IL-13 stimulation. IL-13 altered the staining patterns of TJ proteins and the epithelial morphology. FLG siRNA transfection significantly decreased TEER. The IL-13-mediated reduced esophageal barrier is associated with the altered expression pattern but not with the levels of TJ-associated proteins. A deficiency of FLG altered the stratified epithelial barrier. NEW & NOTEWORTHY Esophageal permeability to small molecules was increased in patients with eosinophilic esophagitis (EoE) and could be induced by IL-13 in our unique air-liquid interface-cultured primary multilayer human esophageal epithelial cells in vitro. A deficiency of filaggrin disrupted the esophageal stratified epithelial barrier. The decreased esophageal barrier in EoE was associated with the altered staining pattern of tight junction proteins, although the levels of the proteins themselves do not appear to be changed.

Download Full-text

Gallotannin Improves the Photoaged-Related Proteins by Extracellular Signal-Regulated Kinases/c-Jun N-Terminal Kinases Signaling Pathway in Human Epidermal Keratinocyte Cells

Journal of Medicinal Food ◽

10.1089/jmf.2017.4096 ◽

2018 ◽

Vol 21 (8) ◽

pp. 785-792 ◽

Cited By ~ 1

Author(s):

Gyoseon Goya M. Ryeom ◽

Weon Jeong Bang ◽

Young Bu Kim ◽

Go Eun Lee

Keyword(s):

Signaling Pathway ◽

Epidermal Keratinocyte ◽

Extracellular Signal ◽

Related Proteins ◽

Human Epidermal Keratinocyte

Download Full-text

Painong San, a Traditional Chinese Compound Herbal Medicine, Restores Colon Barrier Function on DSS-Induced Colitis in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/2810915 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Xuelin Rui ◽

Jiacheng Li ◽

Ye Yang ◽

Li Xu ◽

Yang Liu ◽

...

Keyword(s):

Herbal Medicine ◽

Tight Junction ◽

Barrier Function ◽

Notch Pathway ◽

The Body ◽

Mucosal Barrier ◽

Control Group ◽

Mucosal Permeability ◽

Mucosal Barrier Function ◽

Related Proteins

Objective. The intestinal barrier decreases in colitis and restores the integrity of the mucosal barriers that could be used for the treatment of colitis. Painong San (PNS), a traditional Chinese compound herbal medicine originally recorded in “Jingui Yaolve” by Zhongjing Zhang in the Later Han Dynasty, is often used in China and Japan to treat various purulent diseases including intestinal carbuncle. This study was to investigate the effect of PNS on mucosal barrier function in mice with DSS-induced colitis and its related mechanisms. Methods. BALB/C mice were given 3% DSS to induce colitis. The body weight and stool status of the mice were recorded daily, and the histopathological changes of the colon were observed after execution. The permeability of the intestinal mucosa was measured by fluorescein isothiocyanate-dextran 4000, the change of intestinal microbiota was measured by 16S rDNA, and the tight junction-related proteins and Muc-2 were investigated by immunohistochemical or immunofluorescence. The possible signaling pathways were detected by western blot. Results. Compared with the control group, the composition of the microbiota in the PNS group was close to that of the normal group, the number of goblet cells was improved, and the mucosal permeability was significantly reduced. PNS could upregulate the expression of tight junction-related proteins (ZO-1, claudin-1, and occludin) and Muc-2, and at the same time, regulate the Notch pathway. Conclusion. PNS could effectively improve the mucosal barrier function through multiple ways, including restoring the balance of intestine flora, enhancement of the mucous layer barrier, and mechanical barrier function. These protective effects may relate to inhibiting the Notch signaling pathway activated by DSS.

Download Full-text