Effects of PGE2 EP3/EP4 receptors on bladder dysfunction in mice with experimental autoimmune encephalomyelitis

2013 ◽  
Vol 305 (12) ◽  
pp. F1656-F1662 ◽  
Author(s):  
Rui Xue ◽  
Zhankui Jia ◽  
Xiaomu Kong ◽  
Guofu Pi ◽  
Shengli Ma ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Neurogenic Bladder ◽  
Bladder Dysfunction ◽  
Neurological Impairment ◽  
Receptor Expression ◽  
Bladder Function ◽  
Autoimmune Encephalomyelitis ◽  
Established Method ◽  
Ep Receptor ◽  
Experimental Autoimmune

To investigate the expression of four subtypes of PGE2 E-prostanoid (EP) receptors (EP1–EP4) and the effects of EP3/EP4 on bladder dysfunction in a new neurogenic bladder model induced by experimental autoimmune encephalomyelitis (EAE), the mouse model of EAE was induced using a previously established method, and bladder function in mice with different defined levels of neurological impairment was then examined, including micturition frequencies and voiding weight. Bladders were then harvested for analysis of EP receptor expression by Western blot. Activities of agonists/antagonists of EP3 and EP4 receptors as well as PGE2 were also evaluated at different stages of EAE. The results showed that EAE mice developed profound bladder dysfunction characterized by significantly increased micturition and significantly decreased urine output per micturition. EAE-induced upregulation of EP3 and EP4 receptors in the bladder was accompanied by bladder dysfunction. However, EAE had no significant effect on EP1 and EP2 receptors. Moreover, PGE2 and agonists/antagonists of EP3 and EP4 receptors significantly affected bladder dysfunction in EAE mice. Thus, we believe that EAE mice are useful for investigations of the neurogenic bladder. In addition, EP3 and EP4 receptors play a role in EAE-induced bladder dysfunction, providing us with a new target for the treatment of neurogenic bladders.

scholarly journals Endothelial Microsomal Prostaglandin E Synthetase-1 Upregulates Vascularity and Endothelial Interleukin-1β in Deteriorative Progression of Experimental Autoimmune Encephalomyelitis

2018 ◽  
Vol 19 (11) ◽  
pp. 3647 ◽  
Author(s):  
Takako Takemiya ◽  
Marumi Kawakami ◽  
Chisen Takeuchi
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Vascular Endothelial Cells ◽  
Immunohistochemical Analysis ◽  
Interleukin 1Β ◽  
Prostaglandin E ◽  
Vascular Endothelial ◽  
Autoimmune Encephalomyelitis ◽  
Ep Receptor ◽  
Experimental Autoimmune

Microsomal prostaglandin E synthetase-1 (mPGES-1) is an inducible terminal enzyme for the production of prostaglandin E2 (PGE2). In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mPGES-1 is induced in vascular endothelial cells (VECs) around inflammatory foci and facilitates inflammation, demyelination, and paralysis. Therefore, we investigated the role of CD31-positive VECs in mPGES-1-mediated EAE aggravation using immunohistochemical analysis and imaging of wild-type (wt) and mPGES-1-deficient (mPGES-1−/−) mice. We demonstrated that EAE induction facilitated vascularity in inflammatory lesions in the spinal cord, and this was significantly higher in wt mice than in mPGES-1−/− mice. In addition, endothelial interleukin-1β (IL-1β) production was significantly higher in wt mice than in mPGES-1−/− mice. Moreover, endothelial PGE2 receptors (E-prostanoid (EP) receptors EP1–4) were expressed after EAE induction, and IL-1β was induced in EP receptor-positive VECs. Furthermore, IL-1 receptor 1 expression on VECs was increased upon EAE induction. Thus, increased vascularity is one mechanism involved in EAE aggravation induced by mPGES-1. Furthermore, mPGES-1 facilitated the autocrine function of VECs upon EP receptor induction and IL-1β production, modulating mPGES-1 induction in EAE.

scholarly journals Investigating the mechanism by which the atypical antipsychotic clozapine reduces disease in experimental autoimmune encephalomyelitis

2021 ◽  
Author(s):  
◽  
Pirooz Zareie
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Atypical Antipsychotic ◽  
Antipsychotic Agents ◽  
Receptor Expression ◽  
In Vitro Experiments ◽  
Autoimmune Encephalomyelitis ◽  
Immunological Mechanism ◽  
Atypical Antipsychotic Agents ◽  
Experimental Autoimmune

<p>Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by damage to the myelin sheaths that surround nerve axons. Inflammatory damage to the myelin sheath leads to severe physical disability in patients. Whereas approved disease modifying treatments are available for relapsing-remitting forms of MS, there are no approved treatments for the progressive stages, leaving approximately 50% of MS sufferers without treatment. Therefore, there is an urgent need for development of effective alternatives.  Atypical antipsychotic agents used for treating schizophrenia have recently been recognized for their immune-modifying properties and our laboratory has shown previously that treating mice with risperidone or clozapine reduces the severity of disease in experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Although atypical antipsychotic agents like clozapine have been used in the clinic for almost 60 years, there is very little experimental data that describes the mechanism by which atypical antipsychotic agents like clozapine are able to modify the immune response. This thesis aimed to describe the immunological mechanisms by which clozapine is able to reduce EAE disease and to determine the underlying cellular signalling alterations that occur during treatment to facilitate immune modifying properties.  In vitro experiments showed that clozapine can impair induction of Th1 and Th17 cells while promoting the differentiation of iTreg and increasing Foxp3 expression. However, although clozapine effectively delayed disease onset and reduced the severity of EAE, the therapeutic effect of clozapine was not associated with impaired capacity to induce antigen specific Th1 or Th17 responses in the periphery. Moreover, Treg function was dispensable for disease protection by clozapine. Instead, disease protection by clozapine was associated with a suppressed state of activation in CNS resident microglia and infiltrating monocytes assessed by flow cytometric measurement of activation associated receptor expression. In vitro experiments using primary macrophage cell culture revealed that clozapine can alter the activation of activated macrophages towards a less inflammatory state directly. Interestingly, the altered state of activation in primary macrophages was not associated with detectable changes in cell signalling pathways known to mediate activation.  This thesis demonstrated that clozapine treatment protects from EAE by a multi-faceted immunological mechanism that likely involves modifying multiple pathways and cell types during EAE and may be of therapeutic benefit to MS patients in the progressive stages of disease. Finally, this thesis also has relevance to psychiatry as it demonstrates that clozapine has potential to alter cellular immune responses.</p>

Experimental Autoimmune Encephalomyelitis: CC Chemokine Receptor Expression by Trafficking Cells

2002 ◽  
Vol 19 (4) ◽  
pp. 175-181 ◽  
Author(s):  
Andrzej R. Glabinski ◽  
Bartosz Bielecki ◽  
Sage O'Bryant ◽  
Krzysztof Selmaj ◽  
Richard M. Ransohoff
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Chemokine Receptor ◽  
Receptor Expression ◽  
Autoimmune Encephalomyelitis ◽  
Chemokine Receptor Expression ◽  
Cc Chemokine ◽  
Experimental Autoimmune

scholarly journals Bladder dysfunction in mice with experimental autoimmune encephalomyelitis

2008 ◽  
Vol 203 (1) ◽  
pp. 58-63 ◽  
Author(s):  
Cengiz Z. Altuntas ◽  
Firouz Daneshgari ◽  
Guiming Liu ◽  
Adebola Fabiyi ◽  
Michael Kavran ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Bladder Dysfunction ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

IL-21 receptor expression determines the temporal phases of experimental autoimmune encephalomyelitis

2008 ◽  
Vol 211 (1) ◽  
pp. 14-24 ◽  
Author(s):  
Ruolan Liu ◽  
Ying Bai ◽  
Timothy L. Vollmer ◽  
Xue-Feng Bai ◽  
Youngheun Jee ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Receptor Expression ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune
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