Pro- and anti-inflammatory cytokines regulate the ERK pathway: Implication of the timing for the activation of microglial cells

2005 ◽  
Vol 8 (3-4) ◽  
pp. 277-287 ◽  
Author(s):  
Katherine Saud ◽  
Rodrigo Herrera-Molina ◽  
Rommy Von Bernhardi
2021 ◽  
Vol 11 (11) ◽  
pp. 1482
Author(s):  
Priyanka Chauhan ◽  
Wen S. Sheng ◽  
Shuxian Hu ◽  
Sujata Prasad ◽  
James R. Lokensgard

The role of select pro- and anti-inflammatory mediators in driving microglial cell polarization into classically (M1), or alternatively, (M2) activated states, as well as the subsequent differential responses of these induced phenotypes, was examined. Expression of PD-L1, MHC-II, MHC-I, arginase 1 (Arg-1), and inducible nitric oxide synthase (iNOS) was assessed using multi-color flow cytometry. We observed that both pro- and anti-inflammatory mediators induced PD-L1 expression on non-polarized microglia. Moreover, IFN-γ stimulated significant MHC class I and II expression on these cells. Interestingly, we observed that only IL-4 treatment induced Arg-1 expression, indicating M2 polarization. These M2 cells were refractory to subsequent depolarization and maintained their alternatively activated state. Furthermore, PD-L1 expression was significantly induced on these M2-polarized microglia after treatment with pro-inflammatory mediators, but not anti-inflammatory cytokines. In addition, we observed that only LPS induced iNOS expression in microglial cells, indicating M1 polarization. Furthermore, IFN-γ significantly increased the percentage of M1-polarized microglia expressing iNOS. Surprisingly, when these M1-polarized microglia were treated with either IL-6 or other anti-inflammatory cytokines, they returned to their non-polarized state, as demonstrated by significantly reduced expression of iNOS. Taken together, these results demonstrate differential responses of microglial cells to mediators present in dissimilar microenvironments.


2020 ◽  
Author(s):  
Jiali Chen ◽  
Cailin Tang ◽  
Yang Zhou ◽  
Rongfei Zhang ◽  
Shaoxia Ye ◽  
...  

Abstract Background: Cinnamomum camphora (Linn.) Presl has been widely used in traditional Chinese medicine for a variety of purposes. Our previous study indicated the antibacterial mechanism of the essential oil (EO) from C. camphora; however, the anti-inflammatory activity of EO and its underlying mechanism have not been clearly demonstrated. The present study aims to evaluate the anti-inflammatory principle and mechanism of EO.Methods: The anti-inflammatory activity of EO was evaluated in lipopolysaccharide (LPS)-induced BV2 microglial cells. Nitric oxide (NO) production was measured by NO assay kit. The mRNA expression levels of inducible NO synthase (iNOS), interleukin-6 (IL-6), IL-18 and IL-1β were examined by real time-PCR (RT-PCR). The secretion of pro-inflammatory cytokines in cell supernatants, including IL-6, IL-18 and IL-1β, were assessed by ELISA kits. Furthermore, the metabolic profile of BV2 microglial cells treated with or without EO was explored by GC-MS-based metabolomics analysis. Phosphofructokinase (PFK) and pyruvate kinase (PK) activities were detected by commercial kits.Results: EO significantly decreased the release of NO and the mRNA expression of iNOS in LPS-induced BV2 microglial cells. EO also attenuated LPS-induced increase in the mRNA expression and secretion of inflammatory cytokines including IL-6, IL-18 and IL-1β. 39 metabolites were identified with significantly different contents, including 21 upregulated and 18 downregulated ones, in the metabolomics analysis. Five pathways were enriched by shared differential metabolites. Additionally, compared with the control group, the glucose level was decreased, while the lactate level was increased, in the culture supernatant of LPS-induced BV2 microglia cells, which were reversed by EO treatment. Besides, compared to the LPS-treated group, the activities for PK and PFK in EO group were decreased by 17.59% and 18.23%, respectively.Conclusions: The EO from C. camphora acts as an anti-inflammatory agent, which might be mediated through attenuating the glycolysis capacity of microglial cells.


2008 ◽  
Vol 56 (S 1) ◽  
Author(s):  
W Rees ◽  
T Kubin ◽  
J Pöling ◽  
S Hein ◽  
H Warnecke ◽  
...  

2019 ◽  
Vol 16 (3) ◽  
pp. 251-260 ◽  
Author(s):  
Elaine Wan Ling Chan ◽  
Emilia Tze Ying Yeo ◽  
Kelly Wang Ling Wong ◽  
Mun Ling See ◽  
Ka Yan Wong ◽  
...  

<P>Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments. Objective: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the production of pro-inflammatory mediators. Method: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay. Results: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators. Conclusions: These findings provided evidence that PS root extracts confer neuroprotection against Aβ- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer’s disease (AD).</P>


Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in the hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in the cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells. Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (O-Exo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for stimulation of HepG2 cells in vitro. After 24 h incubation, the protein levels of TNF-α,IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit. Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with control group (P=0.039 and P<0.001 respectively), while significance differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found between three groups in term of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001). Conclusion: These findings suggest that plasma circulating exosomes have probably anti-inflammatory properties independently from body mass index and may decrease the secretion of inflammatory cytokines in liver. However, further investigations in vitro and in vivo are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.


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