The role of the α7nAChR-mediated cholinergic anti-inflammatory pathway in Hirschsprung associated enterocolitis

2020 ◽  
Author(s):  
Feng Chen ◽  
Xiaoyu Wei ◽  
Xiaohua Chen ◽  
Lei Xiang ◽  
Xinyao Meng ◽  
...  
Keyword(s):  
Western Blotting ◽  
Mrna Level ◽  
Underlying Mechanism ◽  
Mrna Levels ◽  
Wild Type ◽  
Inflammatory Pathway ◽  
Anti Inflammatory ◽  
Phosphorylated Stat3 ◽  
Morphology Changes

Abstract Background To investigate the role and the underlying mechanism of the α7nAChR-mediated cholinergic anti-inflammatory pathway in the pathogenesis of Hirschsprung(HSCR) associated enterocolitis（HAEC）. Methods Experimental group:twenty-one-day-old Ednrb-/- mice were selected (n=10), with comparable-age wild type(Ednrb+/+) mice controls (n=10). Intestinal samples were collected. The experimental colons were divided into narrow and dilated segments according to morphology changes. The control colons were divided into distal and proximal segments.Colon HE staining was used to judge HAEC.Acetylcholine levels in colon was measured using enzyme-linked immunosorbent assays. Detected phosphorylated Jak2 (p-Jak2), Jak2, phosphorylated Stat3 (p-Stat3), Stat3, phosphorylated IκBα (p-IκBα) and IκBα were studied by Western blotting; mRNA levels of Jak2, Stat3, and IκBα were detected by RT-qPCR. Results Colon HE staining indicated that HAEC mainly occured in the dilated segments of HSCR mice (Ednrb-/- mice) (EDNRB-P).Acetylcholine content in EDNRB-P was significantly lower than that in the narrow segments (EDNRB-D) (P<0.05). Western blotting showed that the Jak2, p-Jak2, Stat3 and p-Stat3 levels in EDNRB-D were significantly higher than those in EDNRB-P (P<0.05). The p-IκBα and IκBα levels in EDNRB-P were significantly higher than those in EDNRB-D(P<0.05). The mRNA levels of Jak2 and Stat3 in EDNRB-D were higher than those in EDNRB-P, but the IκBα mRNA level was significantly lower than that in EDNRB-P (P<0.05). Conclusions During HAEC, the inflammation in the dilated segment was more severe ,while in the narrow segment there was no obvious inflammatory reaction and the content of acetylcholine was higher, which was associated with the α7nAChR-mediated cholinergic anti-inflammatory pathway.

Role of α2-macroglobulin in fever and cytokine responses induced by lipopolysaccharide in mice

2002 ◽  
Vol 283 (1) ◽  
pp. R218-R226 ◽  
Author(s):  
Alexander V. Gourine ◽  
Valery N. Gourine ◽  
Yohannes Tesfaigzi ◽  
Nathalie Caluwaerts ◽  
Fred Van Leuven ◽  
...  
Keyword(s):  
Mrna Level ◽  
Physiological Role ◽  
Mrna Levels ◽  
Wild Type ◽  
Cytokine Responses ◽  
Α2 Macroglobulin ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

α2-Macroglobulin (α2M) is not only a proteinase inhibitor in mammals, but it is also a specific cytokine carrier that binds pro- and anti-inflammatory cytokines implicated in fever, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). To define the role of α2M in regulation of febrile and cytokine responses, wild-type mice and mice deficient in α2M (α2M −/−) were injected with lipopolysaccharide (LPS). Changes in body temperature as well as plasma levels of IL-1β, IL-6, and TNF-α and hepatic TNF-α mRNA level during fever in α2M −/− mice were compared with those in wild-type control mice. The α2M −/− mice developed a short-term markedly attenuated (ANOVA, P < 0.05) fever in response to LPS (2.5 mg/kg ip) compared with the wild-type mice. At 1.5 h after injection of LPS, the plasma concentration of TNF-α, but not IL-1β or IL-6, was significantly lower (by 58%) in the α2M −/− mice compared with their wild-type controls (ANOVA, P < 0.05). There was no difference in hepatic TNF-α mRNA levels between α2M −/− and wild-type mice 1.5 h after injection of LPS. These data support the hypotheses that 1) α2M is important for the normal development of LPS-induced fever and 2) a putative mechanism of α2M involvement in fever is through the inhibition of TNF-α clearance. These findings indicate a novel physiological role for α2M.

The Role of α7nAChR-Mediated Cholinergic Anti-inflammatory Pathway in Immune Cells

Inflammation ◽  
2021 ◽  
Author(s):  
Yi-jin Wu ◽  
Li Wang ◽  
Chao-fan Ji ◽  
Shao-fei Gu ◽  
Qin Yin ◽  
...  
Keyword(s):  
Immune Cells ◽  
Inflammatory Pathway ◽  
Anti Inflammatory

PGC-1α is associated with C2C12 Myoblast differentiation

2014 ◽  
Vol 9 (11) ◽  
pp. 1030-1036 ◽  
Author(s):  
Yaqiu Lin ◽  
Yanying Zhao ◽  
Ruiwen Li ◽  
Jiaqi Gong ◽  
Yucai Zheng ◽  
...  
Keyword(s):  
Mrna Level ◽  
Biological Significance ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Mrna Levels ◽  
Transfected Cells ◽  
Myosin Heavy Chain Isoform ◽  
Important Mediator

AbstractPGC-1α has been implicated as an important mediator of functional capacity of skeletal muscle. However, the role of PGC-1α in myoblast differentiation remains unexplored. In the present study, we observed a significant up-regulation of PGC-1α expression during the differentiation of murine C2C12 myoblast. To understand the biological significance of PGC-1α up-regulation in myoblast differentiation, C2C12 cells were transfected with murine PGC-1α cDNA and siRNA targeting PGC-1α, respectively. PGC-1α over-expressing clones fused to form typical myotubes with higher mRNA level of myosin heavy chain isoform I (MyHCI) and lower MyHCIIX. No obvious differentiation was observed in PGC-1α-targeted siRNA-transfected cells with marked decrement of mRNA levels of MyHCI and MyHCIIX. Furthermore, PGC-1α increased the expression of MyoD and MyoG in C2C12 cells, which controlled the commitment of precursor cells to myotubes. These results indicate that PGC-1α is associated with myoblast differentiation and elevates MyoD and MyoG expression levels in C2C12 cells.

Transmembrane prolyl 4-hydroxylase is a fourth prolyl 4-hydroxylase regulating EPO production and erythropoiesis

Blood ◽  
2012 ◽  
Vol 120 (16) ◽  
pp. 3336-3344 ◽  
Author(s):  
Anu Laitala ◽  
Ellinoora Aro ◽  
Gail Walkinshaw ◽  
Joni M. Mäki ◽  
Maarit Rossi ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Mrna Level ◽  
Hypoxia Inducible Factor ◽  
Mrna Levels ◽  
Wild Type ◽  
Α Subunit ◽  
Hepcidin Expression ◽  
In The Wild ◽  
Hepcidin Mrna

AbstractAn endoplasmic reticulum transmembrane prolyl 4-hydroxylase (P4H-TM) is able to hydroxylate the α subunit of the hypoxia-inducible factor (HIF) in vitro and in cultured cells, but nothing is known about its roles in mammalian erythropoiesis. We studied such roles here by administering a HIF-P4H inhibitor, FG-4497, to P4h-tm−/− mice. This caused larger increases in serum Epo concentration and kidney but not liver Hif-1α and Hif-2α protein and Epo mRNA levels than in wild-type mice, while the liver Hepcidin mRNA level was lower in the P4h-tm−/− mice than in the wild-type. Similar, but not identical, differences were also seen between FG-4497–treated Hif-p4h-2 hypomorphic (Hif-p4h-2gt/gt) and Hif-p4h-3−/− mice versus wild-type mice. FG-4497 administration increased hemoglobin and hematocrit values similarly in the P4h-tm−/− and wild-type mice, but caused higher increases in both values in the Hif-p4h-2gt/gt mice and in hematocrit value in the Hif-p4h-3−/− mice than in the wild-type. Hif-p4h-2gt/gt/P4h-tm−/− double gene-modified mice nevertheless had increased hemoglobin and hematocrit values without any FG-4497 administration, although no such abnormalities were seen in the Hif-p4h-2gt/gt or P4h-tm−/− mice. Our data thus indicate that P4H-TM plays a role in the regulation of EPO production, hepcidin expression, and erythropoiesis.

Immunomodulatory role of paliperidone in the poly(I:C) model of schizophrenia

2016 ◽  
Vol 33 (S1) ◽  
pp. s220-s221
Author(s):  
K. MacDowell ◽  
E. Munarriz-Cuezva ◽  
D. Martín-Hernández ◽  
A. Sayd ◽  
B. García-Bueno ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Inflammatory Responses ◽  
Poly I:C ◽  
Mrna Levels ◽  
Behavioral Test ◽  
Inflammatory Pathways ◽  
Anti Inflammatory ◽  
Cellular Markers ◽  
Endogenous Antioxidant

IntroductionAlterations on the innate inflammatory response may underlie the pathophysiology of psychiatric diseases, but the mechanisms implicated remain elusive. Current antipsychotics modulate pro/anti-inflammatory pathways, but the specific mechanisms involved remain elusive. One attractive possibility is the regulation of the intracellular signalling pathways of the innate immune receptors Toll-like 3 (TLR3), which triggers antiviral and inflammatory responses.AimsTo elucidate the regulatory role of paliperidone on maternal immune activation (MIA) induced alterations on TLR3 pathway and on the two emerging endogenous antiinflammatory/antioxidant mechanisms NRF2/antioxidant enzymes pathway and the cytokine milieu regulating M1/M2 polarization in microglia.MethodsPregnant mice were treated with the synthetic Toll-like Receptor 3 (TLR3) agonist Poly(I:C) in gestational day 9 and chronically treated with paliperidone (0,05 mg/kg i.p.) in adult offspring. Animals were sacrificed one day after treatment and behavioral test. Inflammation oxidative stress-related mediators were analysed at mRNA and protein level in prefrontal cortex samples. In addition, behavioral test t-maze was conducted.ResultsPaliperidone prevented TLR3 pathway activation and the subsequent MIA-induced neuroinflammatory response. Also, paliperidone induced an increment in the activity and protein expression of nuclear NRF2, as well as increased mRNA levels of the antioxidant enzymes HO1, SOD and catalase in the MIA model. Otherwise, paliperidone increases the antiinflammatory cytokines levels TGFβ and IL-10 in favour of a M2 microglia profile and increased the levels of the M2 cellular markers ArgI and FOLR2.ConclusionsThe modulation of neuroinflammation and enhancement of endogenous antioxidant/anti-inflammatory pathways by current and new antipsychotics could represent an interesting therapeutic strategy for the future.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Micronized Palmitoylethanolamide Ameliorates Methionine- and Choline-Deficient Diet–Induced Nonalcoholic Steatohepatitis via Inhibiting Inflammation and Restoring Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaji Hu ◽  
Hanglu Ying ◽  
Jie Yao ◽  
Longhe Yang ◽  
Wenhui Jin ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Hepatocellular Injury ◽  
Deficient Diet ◽  
Neuroprotective Effects ◽  
Pathway Activation ◽  
Elevated Expression ◽  
Anti Inflammatory

Nonalcoholic steatohepatitis (NASH) has become one of the serious causes of chronic liver diseases, characterized by hepatic steatosis, hepatocellular injury, inflammation and fibrosis, and lack of efficient therapeutic agents. Palmitoylethanolamide (PEA) is an endogenous bioactive lipid with various pharmacological activities, including anti-inflammatory, analgesic, and neuroprotective effects. However, the effect of PEA on nonalcoholic steatohepatitis is still unknown. Our study aims to explore the potential protective role of PEA on NASH and to reveal the underlying mechanism. In this study, the C57BL/6 mice were used to establish the NASH model through methionine- and choline-deficient (MCD) diet feeding. Here, we found that PEA treatment significantly improved liver function, alleviated hepatic pathological changes, and attenuated the lipid accumulation and hepatic fibrosis in NASH mice induced by MCD diet feeding. Mechanistically, the anti-steatosis effect of PEA may be due to the suppressed expression of ACC1 and CD36, elevated expression of PPAR-α, and the phosphorylation levels of AMPK. In addition, hepatic oxidative stress was greatly inhibited in MCD-fed mice treated with PEA via enhancing the expression and activities of antioxidant enzymes, including GSH-px and SOD. Moreover, PEA exerted a clear anti-inflammatory effect though ameliorating the expression of inflammatory mediators and suppressing the NLRP3 inflammasome pathway activation. Furthermore, the impaired autophagy in MCD-induced mice was reactivated with PEA treatment. Taken together, our research suggested that PEA protects against NASH through the inhibition of inflammation and restoration of autophagy. Thus, PEA may represent an efficient therapeutic agent to treat NASH.

scholarly journals The effect of calnexin deletion on the expression level of PDI in Saccharomyces cerevisiae under heat stress conditions

2008 ◽  
Vol 13 (1) ◽  
Author(s):  
Huili Zhang ◽  
Jianwei He ◽  
Yanyan Ji ◽  
Akio Kato ◽  
Youtao Song
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Growth Rate ◽  
Heat Stress ◽  
Protein Expression ◽  
Molecular Chaperone ◽  
Mrna Level ◽  
Stress Conditions ◽  
Mrna Levels ◽  
Wild Type ◽  
Wild Type Yeast

AbstractWe cultured calnexin-disrupted and wild-type Saccharomyces cerevisiae strains under conditions of heat stress. The growth rate of the calnexin-disrupted yeast was almost the same as that of the wild-type yeast under those conditions. However, the induced mRNA level of the molecular chaperone PDI in the ER was clearly higher in calnexin-disrupted S. cerevisiae relative to the wild type at 37°C, despite being almost the same in the two strains under normal conditions. The western blotting analysis for PDI protein expression in the ER yielded results that show a parallel in their mRNA levels in the two strains. We suggest that PDI may interact with calnexin under heat stress conditions, and that the induction of PDI in the ER can recover part of the function of calnexin in calnexin-disrupted yeast, and result in the same growth rate as in wild-type yeast.

Abstract P207: Role of (Pro)Renin Receptor in the Pathogenesis of Colon Cancer

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Akira Nishiyama ◽  
Juan Wang ◽  
Shinichi Yachida ◽  
Genevieve Nguyen ◽  
Takuo Hirose ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Cell Number ◽  
Ductal Adenocarcinoma ◽  
Mrna Levels ◽  
Protein Levels ◽  
Colon Cancer Cell Lines ◽  
Cancer Tissues

(Pro)renin receptor ((P)RR) is a component of the Wnt receptor complex (Science, 2010). We have recently demonstrated that (P)RR plays an important role in the tumorigenesis of pancreatic ductal adenocarcinoma via the activation of Wnt/β-catenin signaling pathway (Shibayama et al. Sci Rep. 2015). Since the patients with colon cancer often show aberrantly activated Wnt/β-catenin-dependent signaling pathway by the mutations of its components, we investigated the possible role of (P)RR and Wnt/β-catenin signaling pathway in carcinogenesis of colon cancer. Real-time PCR was used for measuring mRNA levels of (P)RR. Protein levels of (P)RR was determined by Western blotting and immunohistochemistry. Activated β-catenin levels were determined by Western blotting. Cell proliferative ability was evaluated by counting the cell number in cultured colon cancer cell lines, HCT116 and DLD-1 cells. As compared to normal colon tissues (n=6), mRNA and protein levels of (P)RR were increased by 2.6- and 2.2-fold, respectively, in colon cancer tissues (n=9), which were associated with increased activated β-catenin levels (by 2.8-fold, P<0.05). However, plasma soluble (P)RR levels were not changed in patients with colon cancer (n=9). (P)RR and activated β-catenin levels were also increased in HCT116 (by 2.2- and 2.7-fold, n=5, respectively) and DLD-1 cells (by 1.9- and 2.8-fold, n=5, respectively). In these cells, inhibiting (P)RR with an siRNA attenuated the activity of β-catenin and reduced the proliferative abilities (n=5, P<0.05, respectively). These data suggest that (P)RR contributes to the tumorigenesis of colon cancer through the activation of Wnt/β-catenin signaling pathway.

Abstract 544: Strenuous Exercise and Quercetin Intake Differentially Modulate PCSK9 and ANGPLT4 in Normal C57BL6 Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Halleh Mahini ◽  
Dhuha Alsayrafi ◽  
Tong Wu ◽  
Mahdi Garelnabi
Keyword(s):  
Lipid Metabolism ◽  
Normal Mouse ◽  
Mrna Level ◽  
Exercise Group ◽  
Strenuous Exercise ◽  
Mrna Levels ◽  
Moderate Exercise ◽  
Pcsk9 Gene ◽  
Lipids Metabolism

Introduction: We previously reported that intake of quercetin during moderate exercise modulate lipid metabolism in LDLr -/- C57BL6 mice. The current study investigates the role of strenuous exercise and quercetin on lipids metabolism. Study Design: 40 mice were divided into four groups (10 each). These groups are as follows: Control mice, left untreated; control quercetin group, orally supplied with 100 μg/day of quercetin without exercising; exercise group without quercetin, and exercise group with quercetin supplements. The exercise groups were run on a treadmill for 30 minutes, 20-30m/m/ 5 days/week for two month. All animals were on normal mouse chow, at the end of the two month treatment, tissues were collected and expressions of genes associated lipid metabolism were analyzed and the proteins Western Blotting were determined. Results: PCSK9 mRNA level was significantly up-regulated as the result of combination of exercise and quercetin intake (p< 0.05) or quercetin alone. ANGPLT3 mRNA level did not show any significant changes as a result of exercise or quercetin. However, ANGPLT4 mRNA levels significantly down-regulated with the combination after 8 weeks of exercise and quercetin intake compared to both control and Exercise (p < 0.05). ANGPLT4 also decreased with quercetin intake; however this change is not significant. There was a slight change in ANGPLT 4 levels in the exercise group. Conclusion: The combination of strenuous exercise and quercetin intake did not show any positive affect on LDL (plasma LDL levels were measured; however not presented above), this was also reflected by the upregulation of the PCSK9 gene expression. Lipoprotein related genes differentially modulated with the strenuous exercise and quercetin intake. This data suggest that the combination of strenuous exercise and quercetin intake unfavorably impact LDL associated PCSK9 gene; however differentially affect ANGPLT4 levels with the exercise or the combination.

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