scholarly journals Ferulic acid attenuates microglia-mediated neuroinflammation in retinal degeneration

2020 ◽  
Author(s):  
Xiaowei Sun ◽  
Peng Sun ◽  
Limei Liu ◽  
Pengfei Jiang ◽  
YUANBIN LI
Keyword(s):  
Ferulic Acid ◽  
Retinal Degeneration ◽  
Microglial Activation ◽  
Inflammatory Factors ◽  
Immunomodulatory Activity ◽  
Retinal Structure ◽  
The Impact ◽  
Optimal Protection

Abstract Background: Retinal degeneration is often accompanied by microglia-mediated neuroinflammation. Ferulic acid (FA), an active ingredient of traditional Chinese medicines (TCMs), has been reported to have anti-inflammatory effects. This study explores the impact of FA on microglia-mediated neuroinflammation and associated retinal degeneration in rd10 mice. Methods: Rd10 mice received different concentrations of FA every day from postnatal day (P)4 to P24. On P25, the visual function of the mice was evaluated by electroretinogram, and retinae were collected for further investigation. Microglial activation and the expression of relevant cytokines in the retina were evaluated by qPCR, western blotting and immunofluorescence staining. Retinal structure was assessed by haematoxylin and eosin (HE) staining.Results: Supplementation with 50 mg/kg FA provided optimal protection against retinal degeneration, with treated mice exhibiting more photoreceptor nuclei as well as greater wave amplitude amplification on electroretinogram than untreated mice. FA suppressed microglial activation both in vivo and in vitro, and inhibited the expression of pro-inflammatory factors Tnfα, IL1β, and Ccl2 in the retinae of rd10 mice. Furthermore, FA suppressed the activation of STAT1 and subsequently inhibited IRF8 expression, potentially highlighting a role for these pathways in FA-mediated immunomodulatory activity. Conclusions: Attenuation of neuroinflammation by FA may be beneficial for retarding retinal degeneration.

scholarly journals Ferulic acid attenuates microglia-mediated neuroinflammation in retinal degeneration

2020 ◽  
Author(s):  
Xiaowei Sun ◽  
Peng Sun ◽  
Limei Liu ◽  
Pengfei Jiang ◽  
YUANBIN LI
Keyword(s):  
Ferulic Acid ◽  
Retinal Degeneration ◽  
Microglial Activation ◽  
Inflammatory Factors ◽  
Immunomodulatory Activity ◽  
Retinal Structure ◽  
The Impact ◽  
Optimal Protection

Abstract Background: Retinal degeneration is often accompanied by microglia-mediated neuroinflammation. Ferulic acid (FA), an active ingredient of traditional Chinese medicines (TCMs), has been reported to have anti-inflammatory effects. This study explores the impact of FA on microglia-mediated neuroinflammation and associated retinal degeneration in rd10 mice.Methods: Rd10 mice received different concentrations of FA every day from postnatal day (P)4 to P24. On P25, the visual function of the mice was evaluated by electroretinogram, and retinae were collected for further investigation. Microglial activation and the expression of relevant cytokines in the retina were evaluated by qPCR, western blotting and immunofluorescence staining. Retinal structure was assessed by haematoxylin and eosin(HE) staining. Results: supplementation with 50 mg/kg FA provided optimal protection against retinal degeneration, with treated mice exhibiting more photoreceptor nuclei as well as greater wave amplitude amplification on electroretinogram than untreated mice. FA suppressed microglial activation both in vivo and in vitro, and inhibited the expression of pro-inflammatory factors Tnfα, IL1β, and Ccl2 in the retinae of rd10 mice. Furthermore, FA suppressed the activation of STAT1 and subsequently inhibited IRF8 expression, potentially highlighting a role for these pathways in FA-mediated immunomodulatory activity. Conclusions: Attenuation of neuroinflammation by FA may be beneficial for retarding retinal degeneration.

scholarly journals Ferulic acid attenuates microglia-mediated neuroinflammation in retinal degeneration

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaowei Sun ◽  
Peng Sun ◽  
Limei Liu ◽  
Pengfei Jiang ◽  
Yuanbin Li
Keyword(s):  
Ferulic Acid ◽  
Retinal Degeneration ◽  
Microglial Activation ◽  
Inflammatory Factors ◽  
Immunomodulatory Activity ◽  
Retinal Structure ◽  
The Impact ◽  
Optimal Protection

Abstract Background Retinal degeneration is often accompanied by microglia-mediated neuroinflammation. Ferulic acid (FA), an active ingredient of traditional Chinese medicines (TCMs), has been reported to have anti-inflammatory effects. This study explores the impact of FA on microglia-mediated neuroinflammation and associated retinal degeneration in rd10 mice. Methods Rd10 mice received different concentrations of FA every day from postnatal day (P)4 to P24. On P25, the visual function of the mice was evaluated by electroretinogram, and retinae were collected for further investigation. Microglial activation and the expression of relevant cytokines in the retina were evaluated by qPCR, western blotting and immunofluorescence staining. Retinal structure was assessed by haematoxylin and eosin (HE) staining. Results Supplementation with 50 mg/kg FA provided optimal protection against retinal degeneration, with treated mice exhibiting more photoreceptor nuclei as well as greater wave amplitude amplification on electroretinogram than untreated mice. FA suppressed microglial activation both in vivo and in vitro, and inhibited the expression of pro-inflammatory factors Tnfα, IL1β, and Ccl2 in the retinae of rd10 mice. Furthermore, FA suppressed the activation of STAT1 and subsequently inhibited IRF8 expression, potentially highlighting a role for these pathways in FA-mediated immunomodulatory activity. Conclusions Attenuation of neuroinflammation by FA may be beneficial for retarding retinal degeneration.

scholarly journals Ferulic acid attenuates microglia-mediated neuroinflammation in retinal degeneration

2020 ◽  
Author(s):  
Xiaowei Sun ◽  
Peng Sun ◽  
Limei Liu ◽  
Pengfei Jiang ◽  
YUANBIN LI
Keyword(s):  
Ferulic Acid ◽  
Retinal Degeneration ◽  
Microglia Activation ◽  
Immunofluorescent Staining ◽  
Inflammatory Factors ◽  
Immunomodulatory Activity ◽  
Ccl2 Expression ◽  
The Impact

Abstract Background: To use a rd10 mouse model as a means of exploring the impact of Ferulic acid(FA) on microglia-mediated neuroinflammation as well as associated retinal degeneration. Methods: Rd10 mice received different concentrations of FA treatment every day from postnatal day (P)4 to P24. At P25, mice visual function were detected by electroretinogram, then retinae were collected for further investigation. Retinal microglia activation state and relevant cytokines were evaluated by qPCR, Western blot and immunofluorescent staining. The retinal structure was assessed by HE Staining. Results:50mg/Kg FA supplement exhibited optimal protection against retinal degeneration, with treated mice exhibiting more photoreceptor nuclei as well as significant wave amplitude amplification in electroretinograms. FA suppressed microglia activation both in vivo and in vitro, inhibited pro-inflammatory factors Tnfα, IL1β, Ccl2 expression in rd10 retinae. Furthermore, FA suppressed the activation of STAT1 and subsequently IRF8 expression, potentially highlighting a role for these pathways in FA-mediated immunomodulatory activity. Conclusions: Attenuating neuroinflammation by FA may be beneficial to retard retinal degeneration.

scholarly journals Ferulic acid attenuates microglia-mediated neuroinflammation in retinal degeneration

2020 ◽  
Author(s):  
Xiaowei Sun ◽  
Peng Sun ◽  
Limei Liu ◽  
Pengfei Jiang ◽  
YUANBIN LI
Keyword(s):  
Ferulic Acid ◽  
Retinal Degeneration ◽  
Microglia Activation ◽  
Immunofluorescent Staining ◽  
Inflammatory Factors ◽  
Immunomodulatory Activity ◽  
Ccl2 Expression ◽  
The Impact

Abstract Background : To explore the impact of Ferulic acid (FA) on microglia-mediated neuroinflammation as well as associated retinal degeneration by using a rd10 mouse model as a means. Methods : Rd10 mice received different concentrations of FA treatment every day from postnatal day (P)4 to P24. At P25, mice visual function were detected by electroretinogram, then retinae were collected for further investigation. Retinal microglia activation state and relevant cytokines were evaluated by qPCR, Western blot and immunofluorescent staining. The retinal structure was assessed by HE Staining. Results :50mg/kg FA supplement exhibited optimal protection against retinal degeneration, with treated mice exhibiting more photoreceptor nuclei as well as significant wave amplitude amplification in electroretinograms. FA suppressed microglia activation both in vivo and in vitro , inhibited pro-inflammatory factors Tnfα, IL1β, Ccl2 expression in rd10 retinae. Furthermore, FA suppressed the activation of STAT1 and subsequently IRF8 expression, potentially highlighting a role for these pathways in FA-mediated immunomodulatory activity. Conclusions : Attenuating neuroinflammation by FA may be beneficial to retard retinal degeneration.

scholarly journals Enhanced Suppression of Immune Cells In Vitro by MSC Overexpressing FasL

2020 ◽  
Vol 22 (1) ◽  
pp. 348
Author(s):  
Ana-Maria Vacaru ◽  
Madalina Dumitrescu ◽  
Andrei Mircea Vacaru ◽  
Ioana Madalina Fenyo ◽  
Radu Ionita ◽  
...  
Keyword(s):  
Fas Ligand ◽  
Immunomodulatory Activity ◽  
Proof Of Concept ◽  
Differentiation Potential ◽  
Adenoviral Transduction ◽  
Characteristic Features ◽  
Set Up ◽  
The Impact

Mesenchymal stromal cells (MSC) display several mechanisms of action that may be harnessed for therapeutic purposes. One of their most attractive features is their immunomodulatory activity that has been extensively characterized both in vitro and in vivo. While this activity has proven to be very efficient, it is transient. We aimed to enhance it by transforming MSC to overexpress a first apoptosis signal (Fas) ligand (FasL). In this study, our goal was to induce FasL overexpression through adenoviral transduction in MSC to improve their immunomodulatory activity. We characterized the impact of FasL overexpression on the morphology, proliferation, viability, phenotype, multilineage differentiation potential and immunomodulation of MSC. Moreover, we determined their suppressive properties in mixed reactions with A20 cells, as well as with stimulated splenocytes. Our findings demonstrate that FasL-overexpressing MSC exhibit improved immunosuppressive properties, while maintaining their MSC-characteristic features. In conclusion, we establish, in a proof-of-concept set-up, that FasL-overexpressing MSC represent good candidates for therapeutic intervention targeted at autoimmune disorders.

scholarly journals NOD1/RIP2 signalling enhances the microglia-driven inflammatory response and undergoes crosstalk with inflammatory cytokines to exacerbate brain damage following intracerebral haemorrhage in mice

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Miao Wang ◽  
Xinchun Ye ◽  
Jinxia Hu ◽  
Qiuchen Zhao ◽  
Bingchen Lv ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Brain Damage ◽  
Microglial Activation ◽  
Inflammatory Factors ◽  
Primary Microglia ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background Secondary brain damage caused by the innate immune response and subsequent proinflammatory factor production is a major factor contributing to the high mortality of intracerebral haemorrhage (ICH). Nucleotide-binding oligomerization domain 1 (NOD1)/receptor-interacting protein 2 (RIP2) signalling has been reported to participate in the innate immune response and inflammatory response. Therefore, we investigated the role of NOD1/RIP2 signalling in mice with collagenase-induced ICH and in cultured primary microglia challenged with hemin. Methods Adult male C57BL/6 mice were subjected to collagenase for induction of ICH model in vivo. Cultured primary microglia and BV2 microglial cells (microglial cell line) challenged with hemin aimed to simulate the ICH model in vitro. We first defined the expression of NOD1 and RIP2 in vivo and in vitro using an ICH model by western blotting. The effect of NOD1/RIP2 signalling on ICH-induced brain injury volume, neurological deficits, brain oedema, and microglial activation were assessed following intraventricular injection of either ML130 (a NOD1 inhibitor) or GSK583 (a RIP2 inhibitor). In addition, levels of JNK/P38 MAPK, IκBα, and inflammatory factors, including tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS) expression, were analysed in ICH-challenged brain and hemin-exposed cultured primary microglia by western blotting. Finally, we investigated whether the inflammatory factors could undergo crosstalk with NOD1 and RIP2. Results The levels of NOD1 and its adaptor RIP2 were significantly elevated in the brains of mice in response to ICH and in cultured primary microglia, BV2 cells challenged with hemin. Administration of either a NOD1 or RIP2 inhibitor in mice with ICH prevented microglial activation and neuroinflammation, followed by alleviation of ICH-induced brain damage. Interestingly, the inflammatory factors interleukin (IL)-1β and tumour necrosis factor-α (TNF-α), which were enhanced by NOD1/RIP2 signalling, were found to contribute to the NOD1 and RIP2 upregulation in our study. Conclusion NOD1/RIP2 signalling played an important role in the regulation of the inflammatory response during ICH. In addition, a vicious feedback cycle was observed between NOD1/RIP2 and IL-1β/TNF-α, which could to some extent result in sustained brain damage during ICH. Hence, our study highlights NOD1/RIP2 signalling as a potential therapeutic target to protect the brain against secondary brain damage during ICH.

The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance

2013 ◽  
Vol 150 (3) ◽  
pp. 1024-1031 ◽  
Author(s):  
Mohammad Hossein Boskabady ◽  
Sakine Shahmohammadi Mehrjardi ◽  
Abadorrahim Rezaee ◽  
Houshang Rafatpanah ◽  
Sediqeh Jalali
Keyword(s):  
Zataria Multiflora ◽  
Th2 Cytokine ◽  
Ifn Γ ◽  
The Impact

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

scholarly journals In vitro and in vivo assessment of the protective effect of sufentanil in acute lung injury

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098635
Author(s):  
Qi Gao ◽  
Ningqing Chang ◽  
Donglian Liu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
High Mobility ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Hmgb1 Protein

Objectives To investigate the mechanisms underlying the protective effect of sufentanil against acute lung injury (ALI). Material and Methods Rats were administered lipopolysaccharide (LPS) by endotracheal instillation to establish a model of ALI. LPS was used to stimulate BEAS-2B cells. The targets and promoter activities of IκB were assessed using a luciferase reporter assay. Apoptosis of BEAS-2B cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Results Sufentanil treatment markedly reduced pathological changes in lung tissue, pulmonary edema and secretion of inflammatory factors associated with ALI in vivo and in vitro. In addition, sufentanil suppressed apoptosis induced by LPS and activated NF-κB both in vivo and in vitro. Furthermore, upregulation of high mobility group box protein 1 (HMGB1) protein levels and downregulation of miR-129-5p levels were observed in vivo and in vitro following sufentanil treatment. miR-129-5p targeted the 3ʹ untranslated region and its inhibition decreased promoter activities of IκB-α. miR-129-5p inhibition significantly weakened the protective effect of sufentanil on LPS-treated BEAS-2B cells. Conclusion Sufentanil regulated the miR-129-5p/HMGB1 axis to enhance IκB-α expression, suggesting that sufentanil represents a candidate drug for ALI protection and providing avenues for clinical treatment.

Sign in / Sign up

Export Citation Format

Share Document