Human Urinary Kallidinogenase Reduces Lipopolysaccharide-Induced Neuroinflammation and Oxidative Stress in BV-2 Cells.

Zhongyan Zhao,Zhiyu Xu,Shixiong Huang,Huai Huang,Tao Liu,Xiaoyun Huang

doi:10.1155/2019/6393150

Abstract

Migraine is one of the most common neurological disorders which poses significant socioeconomic burden worldwide. Neuroinflammation and oxidative stress both play important roles in the pathogenesis of migraine. Human urinary kallidinogenase (UK) is a tissue kallikrein derived from human urine. Increasing evidence suggests that UK may protect against ischemic stroke, but UK's treatment potential against migraine remains to be explored. Immortal BV-2 murine microglial cells were treated with UK (125 nM, 250 nM, and 500 nM) and then given lipopolysaccharides (LPS, 1000 ng/mL). Cell viability of BV-2 cells was tested by the CCK-8 assay. Expressions of tumor necrosis factor-α (TNFα), prostaglandin E2 (PGE2), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were examined with the ELISA method and western blot. Intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) were measured to determine oxidative stress. Our results showed that LPS administration increased the levels of proinflammatory cytokines (TNFα, PGE2, IL-6, and IL-1β) and oxidative stress (ROS and MDA) when compared with the control group and decreased significantly upon introduction with UK. Taken together, UK treatment reduced LPS-induced neuroinflammation and oxidative stress in a dose-dependent manner, which might be a potential treatment of migraine.

Highlights

Migraine is one of the most common neurologic disorders and is a major cause of disability worldwide [1]
To examine the cytotoxicity of urinary kallidinogenase (UK) and LPS on BV-2 cells and select the suitable drug concentrations for the subsequent experiments, the effects of UK and LPS on cell viability were detected by the CCK-8 assay
Cell viability of BV-2 cells decreased when the concentration of UK increased to 750 nM and 1000 nM (p < 0.05)

Summary

Introduction

Migraine is one of the most common neurologic disorders and is a major cause of disability worldwide [1]. It is a kind of unilateral pulsating headache with clinical symptoms of nausea, vomiting, phonophobia, and photophobia [2]. Since migraine poses significant socioeconomic burden, looking for new therapies has become an urgent international health priority [4]. E hypothesis that migraine is a neurovascular disorder and the headache is caused by dilation of cerebral and meningeal arteries has been well established [5]. The exact mechanism of migraine is still not well understood. Many research studies have proved that neuroinflammation and oxidative stress played important roles in the pathogenesis of this disease [6, 7]

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Conclusion