scholarly journals Thioperamide Alleviates Lipopolysaccharide-Induced Neuroinflammation and Promotes Neurogenesis by Histamine Dependent Activation of H2R/PKA/CREB Pathway

2021 ◽  
Author(s):  
Jiangong Wang ◽  
Bin Liu ◽  
Fengjiao Sun ◽  
Yong Xu ◽  
Dongmei Zhao ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Inflammatory Response ◽  
Histamine Release ◽  
Cognitive Dysfunction ◽  
Inflammatory Cytokines ◽  
Binding Protein ◽  
Interleukin 4 ◽  
Creb Binding Protein ◽  
Anti Inflammatory ◽  
Creb Pathway

Abstract Background Adult neurogenesis in hippocampus dentate gyrus (DG) is associated with numerous neurodegenerative diseases such as aging and Alzheimer's disease (AD). Overactivation of microglia induced neuroinflammation is well acknowledged to contribute to the impaired neurogenesis in pathologies of these diseases and then leading to cognitive dysfunction. Histamine H3 receptor (H3R) is a presynaptic autoreceptor regulating histamine release via negative feedback way. Recently, studies show that H3R are highly expressed not only in neurons but also in microglia to modulate inflammatory response. However, whether inhibition of H3R is responsible for the neurogenesis and cognition in chronic neuroinflammation induced injury and the mechanism remains unclear. Methods Microglia activity, inflammation and neurogenesis were assessed in vivo by using lipopolysaccharide (LPS) induced model of inflammation. Mice were treated with thioperamide, pyrilamine or cimetidine to evaluate the effect of thioperamide on inflammation and the involving role of histamine. Protein levels of PKA/CREB and NF-κB were assessed to investigate the mechanism by which thioperamide regulate inflammatory response and neurogenesis. The cognitive function was tested by novel object recognition, Y maze and morris water maze. Results In this study, we found that inhibition of H3R by thioperamide reduced the microglia activity and promoted a phenotypical switch from pro-inflammatory M1 to anti-inflammatory M2 in microglia, and ultimately attenuated LPS induced neuroinflammation in mice. Additionally, thioperamide rescued the neuroinflammation induced impairments of neurogenesis and cognitive function. Mechanically, the neuroprotection of thioperamide was involved in histamine dependent H2 receptor (H2R) activation, because cimetidine, an H2R antagonist but not pyrilamine, an H1R antagonist reversed the above effects of thioperamide. Moreover, thioperamide activated the H2R downstream phosphorylated protein kinase A (PKA)/cyclic AMP response element-binding protein (CREB) pathway but inhibited nuclear factor kappa-B (NF-κB) signaling. Activation of CREB by thioperamide promoted interaction of CREB-CREB Binding Protein (CBP) to increase anti-inflammatory cytokines (Interleukin-4 and Interleukin-10) and brain-derived neurotrophic factor (BDNF) release but inhibited NF-κB-CBP interaction to decrease pro-inflammatory cytokines (Interleukin-1β, Interleukin-6 and Tumor necrosis factor α) release. H89, an inhibitor of PKA/CREB signaling, abolished effects of thioperamide on neuroinflammation and neurogenesis. Conclusions Taken together, these results suggested under LPS induced neuroinflammation, the H3R antagonist thioperamide inhibited microglia activity and inflammatory response, and ameliorated impairment of neurogenesis and cognitive dysfunction via enhancing histamine release. Histamine activated H2R and reinforced CREB-CBP interaction but weakened NF-κB-CBP interaction to exert anti-inflammatory effects. This study uncovered a novel histamine dependent mechanism behind the therapeutic effect of thioperamide on neuroinflammation.

scholarly journals Regulation of the Anti-Inflammatory Cytokines Interleukin-4 and Interleukin-10 during Pregnancy

2014 ◽  
Vol 5 ◽  
Author(s):  
Piyali Chatterjee ◽  
Valorie L. Chiasson ◽  
Kelsey R. Bounds ◽  
Brett M. Mitchell
Keyword(s):  
Inflammatory Cytokines ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Anti Inflammatory

scholarly journals Focal intra-colon cooling reduces organ injury and systemic inflammation after REBOA management of lethal hemorrhage in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Awadhesh K. Arya ◽  
Kurt Hu ◽  
Lalita Subedi ◽  
Tieluo Li ◽  
Bingren Hu
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Balloon Catheter ◽  
Organ Injury ◽  
Upper Body ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractResuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia–reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.

scholarly journals Beneficial Effect of Exercise on Cognitive Function during Peripheral Arterial Disease: Potential Involvement of Myokines and Microglial Anti-Inflammatory Phenotype Enhancement

2019 ◽  
Vol 8 (5) ◽  
pp. 653 ◽  
Author(s):  
Marina Leardini-Tristao ◽  
Anne-Laure Charles ◽  
Anne Lejay ◽  
Mégane Pizzimenti ◽  
Alain Meyer ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Peripheral Arterial Disease ◽  
Cognitive Dysfunction ◽  
Arterial Disease ◽  
Public Health Issue ◽  
Information Processing Speed ◽  
Critical Ischemia ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
Peripheral Arterial

Peripheral arterial disease (PAD), leading to intermittent claudication, critical ischemia with rest pain, and/or tissue damage, is a public health issue associated with significant morbidity and mortality. Little is known about the link between PAD, cognitive function, and whether exercise might reduce cognitive dysfunction in PAD patients, as previously observed concerning both quality of life and prognosis. This review highlights the fact that patients suffering from PAD often demonstrate cognitive dysfunction characterized by reduced performance in nonverbal reasoning, reduced verbal fluency, and decreased information processing speed and a greater risk for progression toward dementia. Further, the data presented support that physical exercise, likely through myokine secretion and microglial anti-inflammatory phenotype enhancement, might participate in the cognition protection in common clinical settings.

O1-04-08: Therapeutic application of anti-inflammatory cytokines an Abeta-induced cognitive dysfunction

2008 ◽  
Vol 4 ◽  
pp. T116-T117
Author(s):  
Tsuneya Ikezu ◽  
Tomomi Kiyota ◽  
Masaru Yamamoto ◽  
Jiqing Xu ◽  
Michael T. Jacobsen ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Inflammatory Cytokines ◽  
Therapeutic Application ◽  
Anti Inflammatory

scholarly journals Anti-inflammatory response of IL-4, IL-10 and TGF-β in patients with systemic inflammatory response syndrome

2000 ◽  
Vol 9 (3-4) ◽  
pp. 193-195 ◽  
Author(s):  
Donato Torre ◽  
Roberto Tambini ◽  
Silvana Aristodemo ◽  
Giovanna Gavazzeni ◽  
Antonio Goglio ◽  
...  
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Systemic Inflammatory Response ◽  
Interleukin 4 ◽  
Significant Difference ◽  
Anti Inflammatory

The systemic inflammatory response syndrome (SIRS) is an inflammatory process seen in association with a large number of clinical infective and noninfective conditions.The aim of this study was to investigate the role of anti-inflammatory cytokines such as interleukin–4 (IL–4), interleukin–10 (IL–10), and transforming growth factor-beta (TGF-beta). Serum levels of IL–4, IL–10 and TGF-β were determined in 45 patients with SIRS: 38 patients had SIRS of infectious origin, whereas seven patients had non-infectious SIRS. Twenty healthy subjects were used as controls.Serum levels of IL–4, IL–10 and TGFg were determined by an immunoenzyme assay. A significant increase of IL–4 was observed in these patients at the time of diagnosis and 5 days later. In contrast, serum levels of IL–10 were not increased at the time of diagnosis, but a slight decrease was noted after 5 days. Serum levels of TGF-β were not increased at time of diagnosis, and a slight increase was observed after 5 days. Serum levels of IL–4 were significantly higher in patients with infectious SIRS at the time of diagnosis, whereas no significant difference between infectious and non-infectious SIRS was noted for serum levels of IL–10 and TGF-β at the time of diagnosis and 5 days later.During SIRS, serum levels of IL–4 were significantly increased with a significant correlation between IL–4 and mortality, and only levels of IL–4 were significantly increased in the SIRS caused by infectious stimuli.

scholarly journals Cytokine profile of cervical mucus at different forms of papillomavirus infection

2014 ◽  
Vol 95 (5) ◽  
pp. 642-645
Author(s):  
O V Skidanenko-Levina
Keyword(s):  
Inflammatory Cytokines ◽  
Interleukin 2 ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Epithelial Dysplasia ◽  
Interleukin 4 ◽  
Necrosis Factor Alpha ◽  
Papillomavirus Infection ◽  
Anti Inflammatory ◽  
Cervical Secretion

Aim. To study the levels of pro- and anti-inflammatory cytokines in cervical secretion in females with cervical epithelial dysplasia and latent papillomavirus infection. Methods. The study included 120 females aged 20 to 40 years with cervical papillomavirus infection, who were assigned to two groups using «case-control» method. The first group included 60 females with latent disease, the second group - 60 females with mild and moderate cervical epithelial dysplasia (cervical intraepithelial neoplasia stages I and II). Cytokine levels in cervical secretion were measured by ELISA using «ProCon» test system. Results. ELISA test showed increased levels of interleukin-4 and interleukin-10 (43 [21; 74] and 48 [12; 88] pg/ml, respectively) and decreased levels of interleukin-2 (18.5 [5.5; 27.5] pg/ml), interleukin-6 (0.6 [0.06; 0.9] pg/ml), tumor necrosis factor alpha (88.5 [0; 123] pg/ml), interferon γ (2 [0; 4] pg/ml) in cervical secretion of females with cervical epithelial dysplasia compared to females with latent papillomavirus infection. Thus, females with cervical epithelial dysplasia showed increased levels of anti-inflammatory cytokines: interleukin-4 - by 2.7 times and interleukin-10 - by 2.4 times compared to females with latent disease, while levels of pro-inflammatory cytokines was decreased as following: interleukin-2 - by 1.4 times, interleukin-6 - by 4.5 times, tumor necrosis factor alpha - by 1.8 times, interferon γ - by 6.3 times (p 0.05). Conclusion. Imbalance of immune response cytokine regulation with anti-inflammatory cytokines prevailing might be an important factor facilitating persistence of papillomavirus in cervical epithelium and contributing to cervical epithelial dysplasia onset and progression.

Inhibition of Histamine H3 receptor Attenuates Neuroinflammation and Cognitive Impairments in Alzheimer’s Disease via activating CREB Pathway

2020 ◽  
Author(s):  
Jiangong Wang ◽  
Bin Liu ◽  
Yong Xu ◽  
Chaoyun Wang ◽  
Meizi Yang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Interleukin 4 ◽  
Histamine H3 Receptor ◽  
Creb Phosphorylation ◽  
H3 Receptor ◽  
Age Related ◽  
Anti Inflammatory ◽  
Histamine H3

Abstract BackgroundAlzheimer's disease (AD) is an age-related neurodegenerative disease, which characterized by deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles, neuronal loss, and accompanied by neuroinflammation. Neuroinflammatory processes are well acknowledged to contribute to the progression of AD pathology. Histamine H3 receptor (H3R) is a presynaptic autoreceptor regulating histamine release via negative feedback way. H3R antagonist has been reported to have anti-inflammatory efficacy. However, whether inhibition of H3R is responsible for the anti-neuroinflammation and neuroprotection on APP/PS1 Tg mice remains unclear. MethodsIn this study, microgliosis, astrogliosis, A1 type astrocytes and A2 type astrocytes in APP/PS1 Tg mice were measured by immunostaining by Iba1, GFAP, C3 and S100A10 with and without treatment of thioperamide, an H3R antagonist. Inflammatory response of APP/PS1 Tg mice and effects of thioperamide were studied by measuring levels of pro-inflammatory cytokines (tumor necrosis factor α [TNFα] and interleukin-1β [IL-1β]) and anti-inflammatory cytokines (interleukin-4 [IL-4]). Protein levels of p-CREB and p-P65 NF-kB was tested by western blot to study the mechanism of thioperamide on AD. H89 was applied to study whether the mechanism offered by thioperamide was dependent on CREB activating. The effect of thioperamide and H89 on Aβ deposition was measured by immunostaining and ELISA. The cognitive function was tested by novel object recognition, Y maze and morris water maze. ResultsInhibition of H3R by thioperamide reduced the gliosis and induced a phenotypical switch from A1 to A2 in astrocytes, and ultimately attenuated neuroinflammation in APP/PS1 Tg mice. Additionally, thioperamide rescued the decrease of cyclic AMP response element-binding protein (CREB) phosphorylation and suppressed the phosphorylated nuclear factor kappa B (NF-κB) in APP/PS1 Tg mice. H89, an inhibitor of CREB signaling, abolished these effects of thioperamide to suppress gliosis and proinflammatory cytokine release. Lastly, thioperamide alleviated the deposition of Aβ and cognitive dysfunction in APP/PS1 mice, which were both reversed by administration of H89. ConclusionsTaken together, these results suggested the H3R antagonist thioperamide improved cognitive impairment in APP/PS1 Tg mice via modulation of the CREB-mediated gliosis and inflammation inhibiting, which contributed to Aβ clearance. This study uncovered a novel mechanism involving inflammatory regulating behind the therapeutic effect of thioperamide in AD.

Effect of Electroacupuncture on Spinal Cord Injury in Mice: Inhibition Of Inflammatory Response and Oxidative Stress via ApoE and Nrf2

2020 ◽  
Author(s):  
Ni Dai ◽  
Chenglin Tang ◽  
Hongdi Zhao ◽  
Pan Dai ◽  
Siqin Huang
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Neuroprotective Effect ◽  
Related Factor ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
And Oxidative Stress

Abstract Background: Spinal cord injury (SCI) is a catastrophic central nervous system disease. Inflammatory response and oxidative stress are two critical factors in the pathophysiological process of SCI and closely involved with Apolipoprotein E(ApoE) and Nuclear factor erythroid 2-related factor (Nrf2). Electroacupuncture (EA) has perfectly neuroprotective effect on SCI. However, the underlying mechanism by which EA mediates the inflammatory response and oxidative stress is not completely elucidated. In the present study, we investigated the signaling pathways that EA regulates inflammatory response and oxidative stress through elevation of ApoE and Nrf2 after SCI.Methods: C57BL/6 Wide Type (WT) mice and ApoE -/- mice were subjected to SCI model by a serrefine clamping. Neurological function was detected by BMS scores, ultrastructure of demyelinationed axons was observed by transmission electron microscopy. ApoE, pro- and anti- inflammatory cytokines, oxidative stress-relevant proteins were determined by histochemistry technology. Two-way ANOVA was applied to BMS scores. One-way ANOVA and Bonferroni's multiple comparison test were used to analyse differences among groups.Results: BMS scores were increased gradually and demyelinated axons were improved by EA gradually with the expression of ApoE. EA can inhibit inflammatory response by activation of ApoE, which decreased pro-inflammatory cytokines(TNF-α, IL-6, and IL-1β) expression and increased anti-inflammatory cytokines(IL-10 and TGF-β1).Meanwhile, EA can also inhibit oxidative stress by elevation of Nrf2,which induced HO-1 and NQO1 expression in WT and ApoE -/- mice.Conclusions: EA is a reliable treatment for promoting functional recovery of SCI. Thesynergisticrole of ApoE and Nrf2 in EA regulating inflammatory response and oxidative stress is decisiveto recovery after SCI.

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