Nitric oxide/cyclic GMP signaling regulates motility of a microglial cell line and primary microglia in vitro

Scheiblich, Hannah; Roloff, Frank; Singh, Vikramjeet; Stangel, Martin; Stern, Michael; Bicker, Gerd

doi:10.1016/j.brainres.2014.03.048

Cited by 24 publications

(44 citation statements)

References 65 publications

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“…In fact, P2Y receptors were previously associated with microglia chemotactic function to ATP [69]. Reduced ability to migrate towards LPS was also a feature of our M1 polarized N9 cells, although there is some controversy on the ability of LPS to induce or inhibit migration [45, 70, 71], since it may depend on LPS concentration and on mediators released by the activated microglia near the site of injury [72]. …”

Section: Discussionmentioning

confidence: 86%

Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization

Cunha

Gomes

Vaz

et al. 2016

Mediators of Inflammation

133

109

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Identification of mediators triggering microglia activation and transference of noncoding microRNA (miRNA) into exosomes are critical to dissect the mechanisms underlying neurodegeneration. We used lipopolysaccharide- (LPS-) induced N9 microglia activation to explore new biomarkers/signaling pathways and to identify inflammatory miRNA (inflamma-miR) in cells and their derived exosomes. Upregulation of iNOS and MHC-II (M1-markers) and downregulation of arginase 1, FIZZ1 (M2-markers), and CX3CR1 (M0/M2 polarization) confirmed the switch of N9 LPS-treated cells into the M1 phenotype, as described for macrophages/microglia. Cells showed increased proliferation, activated TLR4/TLR2/NF-κB pathway, and enhanced phagocytosis, further corroborated by upregulated MFG-E8. We found NLRP3-inflammasome activation in these cells, probably accounting for the increased extracellular content of the cytokine HMGB1 and of the MMP-9 we have observed. We demonstrate for the first time that the inflamma-miR profiling (upregulated miR-155 and miR-146a plus downregulated miR-124) in M1 polarized N9 cells, noticed by others in activated macrophages/microglia, was replicated in their derived exosomes, likely regulating the inflammatory response of recipient cells and dissemination processes. Data show that LPS-treated N9 cells behave like M1 polarized microglia/macrophages, while providing new targets for drug discovery. In particular, the study yields novel insights into the exosomal circulating miRNA during neuroinflammation important for emerging therapeutic approaches targeting microglia activation.

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Section: Discussionmentioning

confidence: 86%

Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization

Cunha

Gomes

Vaz

et al. 2016

Mediators of Inflammation

133

109

View full text Add to dashboard Cite

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“…The action of sildenafil in improving the clinical status of patients with MS was initially attributed to the induction of neurogenesis; however, recent data has suggested that sildenafil is a modulator of inflammation in the central and peripheral nervous system and protects the myelin sheath both in pathological and healthy conditions (Nunes et al, 2012;Pifarre et al, 2011;Raposo et al, 2013, Garcia et al, 2014. Furthermore, intracellular accumulation of cGMP in different models of inflammation reduces production of pro-inflammatory cytokines such as IFN-γ, TNF-α and interleukins (ILs), and reduces oxidative stress, modulating inflammatory response (Scheiblich et al, 2014). In addition, inhibition of PDEs appears to block the inflammatory response of microglia, reducing changes to the BRES : …”

Section: Discussionmentioning

confidence: 97%

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model

et al. 2015

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“…Intracellular cGMP increases can, thus, lead to cAMP accumulation (Beavo, 1995;Degerman et al, 1997;Maurice and Haslam, 1990). Because nitric oxide (NO) is a strong inducer of cGMP through guanylate cyclase stimulation and NO has been shown to modulate microglial motility in a cGMP-dependent manner in in vitro and in vivo models (Dibaj et al, 2010;Duan et al, 2009;Scheiblich et al, 2014), we tested whether NO-dependent cGMP increase drives filopodia growth.…”

Section: Endogenous Camp-increasing Pathways Trigger Microglial Filopmentioning

confidence: 99%

Nanoscale Surveillance of the Brain by Microglia via cAMP-Regulated Filopodia

et al. 2019

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Article Nanoscale Surveillance of the Brain by Microglia via cAMP-Regulated Filopodia Graphical Abstract Highlights d Microglia use actin-dependent filopodia to efficiently sample the brain parenchyma d Intracellular cAMP drives filopodia growth but induces large process retraction d Norepinephrine and nitric oxide contribute to cAMP-driven filopodia extension d Fine filopodia and large processes establish dual-scale surveillance by microglia This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). relative to variations in the brain parenchyma environment. STAR+METHODSDetailed methods are provided in the online version of this paper and include the following:TABLE d CONTACT FOR REAGENTS AND RESOURCE SHARING d EXPERIMENTAL MODEL AND SUBJECT DETAILS B Animals B Acute slice preparation and maintenance B Isolation of rat microglia d METHOD DETAILS B Open cranial window surgery and in vivo two-photon imaging B Brain perfusion, immunofluorescence and confocal imaging B Acute slice two-photon imaging B Slice fixation and immunolabelling B Rat primary microglia live imaging B Western blotting d QUANTIFICATION AND STATISTICAL ANALYSIS B Image processing and analysis B Statistical analysis SUPPLEMENTAL INFORMATION Supplemental Information can be found online at https://doi.

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Nitric oxide/cyclic GMP signaling regulates motility of a microglial cell line and primary microglia in vitro

Cited by 24 publications

References 65 publications

Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization

Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model

Nanoscale Surveillance of the Brain by Microglia via cAMP-Regulated Filopodia

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