Biomedical subjects

Yiheng Xie

Publications and source records attributed to Yiheng Xie.

4 recordsLinked to original sources

PubMed2004

Inflammatory mediators and growth factors in the spinal cord of G93A SOD1 rats.

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. One mechanism involved in ALS pathology is neuroinflammation. Neuroinflammation is mediated by soluble pro-inflammatory molecules such as cytokines, prostaglandins and nitric oxide. Studies on transgenic mice demonstrated the expression of pro-inflammatory mediators in early stages of murine ALS. Recently a transgenic rat model became available. Since species differences in regard to cytokine expression have been reported in other disease models we set out to validate the neuroinflammatory hypothesis in the ALS-transgenic rat. We investigated the expression of inflammatory mediators and growth factors in the spinal cord by semi-quantitative RT-PCR. We found that several pro-inflammatory mediators are up-regulated at asymptomatic and end-stages, whereas VEGF, a neuroprotective factor was down-regulated.

Amyotrophic Lateral Sclerosis↗

PubMed2004

The microglia-activating potential of thrombin: the protease is not involved in the induction of proinflammatory cytokines and chemokines.

The serine protease thrombin is known as a blood coagulation factor. Through limited cleavage of proteinase-activated receptors it can also control growth and functions in various cell types, including neurons, astrocytes, and microglia (brain macrophages). A number of previous studies indicated that thrombin induces the release of proinflammatory cytokines and chemokines from microglial cells, suggesting another important role for the protease beyond hemostasis. In the present report, we provide evidence that this effect is not mediated by any proteolytic or non-proteolytic mechanism involving thrombin proper. Inhibition of the enzymatic thrombin activity did not affect the microglial release response. Instead the cyto-/chemokine-inducing activity solely resided in a high molecular weight protein fraction that could be isolated in trace amounts even from apparently homogenous alpha- and gamma-thrombin preparations. High molecular weight material contained thrombin-derived peptides as revealed by mass spectrometry but was devoid of thrombin-like enzymatic activity. Separated from the high molecular weight fraction by fast protein liquid chromatography, enzymatically intact alpha- and gamma-thrombin failed to trigger any release. Our findings may force a revision of the notion that thrombin itself is a direct proinflammatory release signal for microglia. In addition, they could be relevant for the study of other cellular activities and their assignment to this protease.

Amino Acid Sequence↗

PubMed2003

Expression of proteinase-activated receptors in mouse microglial cells.

Microglia are the resident immune cells of the CNS: they are activated rapidly by CNS damage and perform the function of tissue macrophages. The first steps during microglial activation are currently under intense study, and it is widely believed that substances released from damaged brain tissue can trigger this process. We recently reported that the blood coagulation factor thrombin, which enters the CNS during breakdown of the blood-brain barrier, activates microglial cells. The cellular effects of thrombin and trypsin-like proteases are mediated by proteinase-activated receptors (PARs). Based on our prior data we hypothesized that microglial cells express these receptors. Using RT-PCR and flow cytometry, we report that primary mouse microglial cells, as well as the murine microglial cell lines BV-2 and N9, indeed express PARs, albeit at different levels. Demonstrating multiple PARs on microglia may enhance the attractiveness of PARs as therapeutic targets in neuroinflammatory disorders.

Animals↗

PubMed2003

Nonpsychotropic cannabinoid receptors regulate microglial cell migration.

During neuroinflammation, activated microglial cells migrate toward dying neurons, where they exacerbate local cell damage. The signaling molecules that trigger microglial cell migration are poorly understood. In this paper, we show that pathological overstimulation of neurons by glutamate plus carbachol dramatically increases the production of the endocannabinoid 2-arachidonylglycerol (2-AG) but only slightly increases the production of anandamide and does not affect the production of two putative endocannabinoids, homo-gamma-linolenylethanolamide and docosatetraenylethanolamide. We further show that pathological stimulation of microglial cells with ATP also increases the production of 2-AG without affecting the amount of other endocannabinoids. Using a Boyden chamber assay, we provide evidence that 2-AG triggers microglial cell migration. This effect of 2-AG occurs through CB2 and abnormal-cannabidiol-sensitive receptors, with subsequent activation of the extracellular signal-regulated kinase 1/2 signal transduction pathway. It is important to note that cannabinol and cannabidiol, two nonpsychotropic ingredients present in the marijuana plant, prevent the 2-AG-induced cell migration by antagonizing the CB2 and abnormal-cannabidiol-sensitive receptors, respectively. Finally, we show that microglial cells express CB2 receptors at the leading edge of lamellipodia, which is consistent with the involvement of microglial cells in cell migration. Our study identifies a cannabinoid signaling system regulating microglial cell migration. Because this signaling system is likely to be involved in recruiting microglial cells toward dying neurons, we propose that cannabinol and cannabidiol are promising nonpsychotropic therapeutics to prevent the recruitment of these cells at neuroinflammatory lesion sites.

Animals↗