Anti-colonic Inflammation by Black Raspberries through Regulating Toll-like Receptor-4 Signaling in Interlukin-10 Knockout Mice

Inflammation is emerging as a critical factor in the pathophysiology of intracranial aneurysm. TLR4 (toll-like receptor 4) contributes not only to the innate immune responses but also to the inflammatory processes associated with vascular disease. Therefore, we examined the contribution of the TLR4 pathway to the development of the rupture of intracranial aneurysm. We used a mouse model of intracranial aneurysm. TLR4 inhibition significantly reduced the development of aneurysmal rupture. In addition, the rupture rate and levels of proinflammatory cytokines were lower in TLR4 knockout mice than the control littermates. Macrophage/monocyte-specific TLR4 knockout mice had a lower rupture rate than the control littermate mice. Moreover, the deficiency of MyD88 (myeloid differentiation primary-response protein 88), a key mediator of TLR4, reduced the rupture rate. These findings suggest that the TLR4 pathway promotes the development of intracranial aneurysmal rupture by accelerating inflammation in aneurysmal walls. Inhibition of the TLR4 pathway in inflammatory cells may be a promising approach for the prevention of aneurysmal rupture and subsequent subarachnoid hemorrhage.

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The role of Toll-like receptor 4 in apoptosis of brain tissue after induction of intracerebral hemorrhage

Journal of Neuroinflammation ◽

10.1186/s12974-019-1634-x ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 4

Author(s):

Xiaowei Fei ◽

Yeting He ◽

Jia Chen ◽

Weitao Man ◽

Chen Chen ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Knockout Mice ◽

Neuronal Apoptosis ◽

Inflammatory Factors ◽

Toll Like Receptor ◽

Wild Type ◽

Toll Like Receptor 4 ◽

Tnf Α ◽

Apoptotic Effect

Abstract Background Inflammation and apoptosis caused by intracerebral hemorrhage (ICH) are two important factors that affect patient prognosis and survival. Toll-like receptor 4 (TLR4) triggers activation of the inflammatory pathway, causing synthesis and release of inflammatory factors. The inflammatory environment also causes neuronal apoptosis. However, no studies have reported the role of TLR4 in inflammation and apoptosis. Methods We performed survival curve analysis and behavioral scores on TLR4 knockout mice and wild-type mice after inducing ICH. We used TLR4 knockout mice and wild-type mice to make ICH models with type VII collagenase and explored the link between TLR4 in inflammation and apoptosis. We used Western blot to detect the expression of apoptosis-related proteins, inflammatory factors, and their receptors at different time points after ICH induction. The effects of TLR4 on apoptosis were observed by TUNEL, Hoechst, and HE staining techniques. The association with TLR4 in inflammation and apoptosis was explored using IL-1β and TNF-α antagonists. Data conforming to a normal distribution are expressed as mean ± standard deviation. Grade and quantitative data were compared with rank sum test and t test between two groups. P < 0.05 was considered statistically significant. Results TLR4 knockout significantly increased the survival rate of ICH mice. The scores of TLR4 knockout mice were significantly lower than those of wild-type mice. We found that TLR4 knockout mice significantly inhibited apoptosis and the expression of inflammatory factors after the induction of ICH. The apoptosis of ICH-induced mice was significantly improved after injecting IL-1β and TNF-α antagonists. Moreover, the anti-apoptotic effect of the antagonist in wild-type mice is more pronounced. A single injection of the antagonist failed to improve apoptosis in TLR4 knockout mice. Conclusions We conclude that TLR4-induced inflammation after ICH promotes neuronal apoptosis. IL-1β and TNF-α antagonists attenuate this apoptotic effect. Therefore, targeting TLR4 in patients with clinical ICH may attenuate inflammatory response, thereby attenuating apoptosis and improving prognosis.

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Curcumin Protects against Atherosclerosis in Apolipoprotein E-Knockout Mice by Inhibiting Toll-like Receptor 4 Expression

Journal of Agricultural and Food Chemistry ◽

10.1021/acs.jafc.7b04260 ◽

2018 ◽

Vol 66 (2) ◽

pp. 449-456 ◽

Cited By ~ 25

Author(s):

Shanshan Zhang ◽

Jun Zou ◽

Peiyang Li ◽

Xiumei Zheng ◽

Dan Feng

Keyword(s):

Apolipoprotein E ◽

Knockout Mice ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Apolipoprotein E Knockout Mice

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Effects of Chronic Mild Stress on the Development of Atherosclerosis and Expression of Toll-Like Receptor 4 Signaling Pathway in Adolescent Apolipoprotein E Knockout Mice

Journal of Biomedicine and Biotechnology ◽

10.1155/2009/613879 ◽

2009 ◽

Vol 2009 ◽

pp. 1-13 ◽

Cited By ~ 16

Author(s):

Hongfeng Gu ◽

Chaoke Tang ◽

Kuang Peng ◽

Hui Sun ◽

Yongzong Yang

Keyword(s):

Apolipoprotein E ◽

Signaling Pathway ◽

Knockout Mice ◽

Chronic Mild Stress ◽

Mild Stress ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Apolipoprotein E Knockout Mice ◽

Tlr4 Signaling Pathway ◽

Myeloid Differentiation Factor

Here, we investigated the effect of chronic mild stress (CMS) on the development of atherosclerosis as well as the expression of Toll-like receptors (TLRs) signaling pathway in adolescent apolipoprotein E knockout (apoE-/-) mice. Mice were subjected to daily CMS for 0, 4, and 12 weeks, respectively. To identify the expression of Toll-like receptor 4 signaling pathway in adolescent apolipoprotein E knockout mice subjected to CMS, we compared gene expression in aortas of stressed and unstressed mice using TLRs signaling pathway real-time PCR microarrays consisting of 87 genes. We found that atherosclerosis lesions both in aortic tress and sinuses of CMS mice were significantly increased linearly in response to duration of CMS exposure. Among 87 genes analyzed, 15 genes were upregulated in stressed mice, especially TLR4, myeloid differentiation factor 88 (MyD88), and IL-1β, and 28 genes were downregulated compared with nonstressed mice. CMS mice demonstrated markedly increased aortic atherosclerosis that were associated with significant increases in levels of expression of TLR4, MyD88, nuclear factorκB (NF-κB), MCP-1, IL-1β, TNF-α, and sICAM-1. Taken together, our results suggest an important role for TLR4 signaling pathway in atherosclerosis in a CMS mouse model.

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