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Journal of Inflammation
Published in: Journal of Inflammation 1/2018

Open Access 01-12-2018 | Research

Interleukin-10 attenuates impairment of the blood-brain barrier in a severe acute pancreatitis rat model

Authors: Ronggui Lin, Fei Chen, Shi Wen, Tianhong Teng, Yu Pan, Heguang Huang

Published in: Journal of Inflammation | Issue 1/2018

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Abstract

Background

Impairment of the blood-brain barrier (BBB) in severe acute pancreatitis (SAP) could result in life-threatening pancreatic encephalopathy. Interleukin-10 (IL-10) is a classical cytokine that is well-known for its strong immunoregulatory and anti-inflammatory abilities. However, whether and how IL-10 protects the BBB in SAP are still unclear.

Methods

This study includes in vivo experiments using a SAP rat model and in vitro experiments using an in vitro BBB model consisting of a monolayer of brain microvascular endothelial cells (BMECs). The study groups are divided into the control, SAP (in vivo)/TNF-α (in vitro), IL-10 treatment, IL-10 + signal transducer and activator of transcription 3 (STAT3) inhibitor S3I-201 treatment groups. Pancreatic pathological scores, serum amylase, serum TNF-α levels and BBB permeability by Evan’s blue assay in SAP rat models were evaluated. BMEC apoptosis in SAP rats or induced by TNF-αin vitro was detected by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and flow cytometry, separately. Expression levels of claudin-5 and proteins involved in the STAT3 signaling pathway were measured by Western blotting. Location and changes of junctional structure of claudin-5 on BMECs were assessed by immunohistochemistry and immunofluorescence.

Results

In vivo, IL-10 alleviated the severity of inflammation, attenuated the increased BBB permeability in SAP rat models by reducing BMEC apoptosis via the STAT3 pathway and ameliorated the down-regulation of claudin-5 expression in BMECs; in vitro, IL-10 improved BBB integrity against TNF-α by attenuating BMEC apoptosis via the STAT3 pathway, the impairment of tight junction structure and the down-regulation of claudin-5 expression in BMECs.

Conclusions

IL-10 improves BBB properties in SAP by attenuating the down-regulation of claudin-5 expression and the impairment of tight junctions and by STAT3 pathway-mediated anti-apoptotic effects on BMECs.
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Metadata
Title
Interleukin-10 attenuates impairment of the blood-brain barrier in a severe acute pancreatitis rat model
Authors
Ronggui Lin
Fei Chen
Shi Wen
Tianhong Teng
Yu Pan
Heguang Huang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2018
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/s12950-018-0180-0

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