Luteolin reduces inflammation in Staphylococcus aureus-induced mastitis by inhibiting NF-kB activation and MMPs expression.

Ying-fang Guo,Weijing Sun,Yifan Zhao,Meng-yao Guo,Nian-nian Xu,Cheng-ye Li

doi:10.18632/oncotarget.16092

Ying-fang Guo, Weijing Sun + Show 4 more

Open Access

https://doi.org/10.18632/oncotarget.16092

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Journal: Oncotarget	Publication Date: Mar 10, 2017
Citations: 50	License type: cc-by

Affiliation: Huazhong Agricultural University

Abstract

Mastitis is a serious and prevalent disease caused by infection by pathogens such as Staphylococcus aureus. We evaluated the anti-inflammatory effects and mechanism of luteolin, a natural flavonoid with a wide range of pharmacological activities, in a mouse model of S. aureus mastitis. We also treated cultured mouse mammary epithelial cells (mMECs) with S. aureus and luteolin. Histopathological changes were examined by H&E staining and the levels of inflammatory cytokine proteins were analyzed using ELISAs. We determined mRNA levels with qPCR and the level of NF-κB and matrix metalloproteinase (MMP) proteins by Western blotting. The observed histopathological changes showed that luteolin protected mammary glands with S. aureus infection from tissue destruction and inflammatory cell infiltration. Luteolin inhibited the expression of TNF-α, IL-1β, and IL-6, all of which were increased with S. aureus infection of mammary tissues and mMECs. S. aureus-induced TLR2 and TLR4 was suppressed by luteolin, as were levels of IκBα and NF-κB p65 phosphorylation and expression of MMP-2 and MMP-9. Levels of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 were enhanced. These findings suggest luteolin is a potentially effective new treatment to reduce tissue damage and inflammation from S. aureus-induced mastitis.

Highlights

Mastitis, initially defined as an inflammatory response of the mammary glands caused by invading bacteria, is a serious disease for both humans and animals [1]
Luteolin inhibited the expression of tumor necrosis factor-α (TNF-α), IL-1β, and IL-6, all of which were increased with S. aureus infection of mammary tissues and mammary epithelial cells (mMECs)
NF-κB and inflammatory cytokines regulate the expression of matrix metalloproteinases (MMPs) and its inhibitor tissue inhibitor of metalloproteinases (TIMPs) [13, 14]

Summary

Introduction

Initially defined as an inflammatory response of the mammary glands caused by invading bacteria, is a serious disease for both humans and animals [1]. Local innate immunity plays a key role in initiating and coordinating homeostasis and resistance to intramammary infection by regulating effector cytokines and other mediators of inflammation [5]. A previous study showed that mouse mammary epithelial cell (mMECs) recognition of the infection through the activation of several pattern recognition receptors (PRRs) is necessary for the initiation of the immune response in the mammary glands [6]. Once S. aureus infects the mammary glands, these receptors induce innate immune by producing mediators of inflammation and local defense [7]. TLR-2 is activated by several classes of microorganisms such as peptidoglycan and lipoteichoic acid, which are major components of the cell wall pathogen-associated molecular pattern (PAMP) of Gram-positive bacteria, including S. aureus [9]. Increased expression of MMPs has been associated with the inflammatory process [15]

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