Lipid rafts in glial cells: role in neuroinflammation and pain processing

Activation of microglia and astrocytes secondary to inflammatory processes contributes to the development and perpetuation of pain with a neuropathic phenotype. This pain state presents as a chronic debilitating condition and affects a large population of patients with conditions like rheumatoid arthritis and diabetes, or after surgery, trauma, or chemotherapy. Here, we review the regulation of lipid rafts in glial cells and the role they play as a key component of neuroinflammatory sensitization of central pain signaling pathways. In this context, we introduce the concept of an inflammaraft (i-raft), enlarged lipid rafts harboring activated receptors and adaptor molecules and serving as an organizing platform to initiate inflammatory signaling and the cellular response. Characteristics of the inflammaraft include increased relative abundance of lipid rafts in inflammatory cells, increased content of cholesterol per raft, and increased levels of inflammatory receptors, such as toll-like receptor (TLR)4, adaptor molecules, ion channels, and enzymes in lipid rafts. This inflammaraft motif serves an important role in the membrane assembly of protein complexes, for example, TLR4 dimerization. Operating within this framework, we demonstrate the involvement of inflammatory receptors, redox molecules, and ion channels in the inflammaraft formation and the regulation of cholesterol and sphingolipid metabolism in the inflammaraft maintenance and disruption. Strategies for targeting inflammarafts, without affecting the integrity of lipid rafts in noninflammatory cells, may lead to developing novel therapies for neuropathic pain states and other neuroinflammatory conditions.

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Caveolin-1, galectin-3 and lipid raft domains in cancer cell signalling

Essays in Biochemistry ◽

10.1042/bse0570189 ◽

2015 ◽

Vol 57 ◽

pp. 189-201 ◽

Cited By ~ 13

Author(s):

Jay Shankar ◽

Cecile Boscher ◽

Ivan R. Nabi

Keyword(s):

Plasma Membrane ◽

Lipid Rafts ◽

Cancer Cell ◽

Cellular Response ◽

Spatial Organization ◽

Essential Feature ◽

Cell Signalling ◽

Coated Pits ◽

Signalling Molecules ◽

Raft Domains

Spatial organization of the plasma membrane is an essential feature of the cellular response to external stimuli. Receptor organization at the cell surface mediates transmission of extracellular stimuli to intracellular signalling molecules and effectors that impact various cellular processes including cell differentiation, metabolism, growth, migration and apoptosis. Membrane domains include morphologically distinct plasma membrane invaginations such as clathrin-coated pits and caveolae, but also less well-defined domains such as lipid rafts and the galectin lattice. In the present chapter, we will discuss interaction between caveolae, lipid rafts and the galectin lattice in the control of cancer cell signalling.

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Augmentation of neuronal excitability by glial cells in the rat spinal dorsal horn under persistent pain state revealed by optical imaging with voltage-sensitive dye

Neuroscience Research ◽

10.1016/j.neures.2011.07.686 ◽

2011 ◽

Vol 71 ◽

pp. e159

Author(s):

Misato Murayama ◽

Hiroshi Ikeda ◽

Kazuyuki Murase

Keyword(s):

Optical Imaging ◽

Dorsal Horn ◽

Glial Cells ◽

Spinal Dorsal Horn ◽

Neuronal Excitability ◽

Persistent Pain ◽

Voltage Sensitive Dye ◽

Spinal Dorsal ◽

Pain State

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Abstract 46: High-Density Lipoproteins Control Monocyte Differentiation Through microRNA Intercellular Communication

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a46 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Kasey C Vickers ◽

Michael G Levin ◽

Michael P Anderson ◽

Qing Xu ◽

Joshua Anzinger ◽

...

Keyword(s):

Gene Expression ◽

Rna Sequencing ◽

High Throughput ◽

Small Rna ◽

Cellular Response ◽

Culture Media ◽

Recipient Cell ◽

Inflammatory Cells ◽

High Density Lipoproteins ◽

Small Rna Sequencing

Many HDL-microRNAs (miRNA) are well-characterized post-transcriptional regulators of inflammation, and are significantly increased on HDL with hypercholesterolemia and atherosclerosis in humans and mice. Therefore, we hypothesize that inflammatory cells uniquely control their own gene expression through cellular miRNA export to HDL and then regulate recipient cell gene expression through HDL-mediated miRNA delivery. To test this hypothesis, we used high-throughput proteomics, Open Arrays, small RNA sequencing, and gene expression microarrays. Human monocytes (plasma elutriation) were differentiated into dendritic cells and multiple macrophage phenotypes. Each cell-type was incubated with pure reconstituted HDL (rHDL), which was then purified from culture media by apolipoprotein A-I immunoprecipitation after 24 h, and both cellular and HDL-miRNAs were profiled using TaqMan Open Arrays. Macrophages were found to export high levels of miRNAs to HDL that inhibit monocyte/macrophage differentiation (miR-146a, miR-223); however, monocytes were also found to export many miRNAs associated with differentiation, including miR-92a, miR-222, miR-17, miR-20a, miR106a, and miR-21. Furthermore, many miRNAs were found to be transcribed in inflammatory cells, but completely exported to HDL and not retained in the cell. Most interestingly, HDL treatment was found to induce miR-223 transcription in monocytes, as determined by primary miR-223 transcript levels; however, intracellular levels of the mature form (miR-223) did not change. These results suggest that HDL induces the export of miRNAs it transports. PAR-CLIP with high-throughput small RNA sequencing was used to demonstrate that miRNAs are transferred from macrophages to endothelial cells and loaded onto cellular Argonaute 2-continaining RNA-induced silencing complexes. To demonstrate this in mice, human HDL, containing endogenous levels of miR-223, were injected into miR-223-null mice and inflammation-associated miRNA delivery was mapped in vivo. In summary, we found profound differences in the cellular response to HDL treatment and HDL-miRNA communication amongst inflammatory cell phenotypes that are physiologically relevant to cardiovascular disease.

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Targeting of ion channels to membrane microdomains: localization of KV channels to lipid rafts

Trends in Pharmacological Sciences ◽

10.1016/j.tips.2003.11.007 ◽

2004 ◽

Vol 25 (1) ◽

pp. 16-21 ◽

Cited By ~ 126

Author(s):

Jeffrey R Martens ◽

Kristen O'Connell ◽

Michael Tamkun

Keyword(s):

Ion Channels ◽

Lipid Rafts ◽

Membrane Microdomains ◽

Kv Channels

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THE EFFECT OF CALCIUM HYDROXIDE-PROPOLIS ON THE NUMBER OF MACROFAG CELLS ON THE WISTAR RAT DENTAL WITH PULPA PERFORMANCE

Conservative Dentistry Journal ◽

10.20473/cdj.v10i2.2020.58-61 ◽

2020 ◽

Vol 10 (2) ◽

pp. 58

Author(s):

Setyabudi Setyabudi ◽

Devi Eka Juniarti ◽

Ira Widjiastuti ◽

Maughfirah Shintya Fathori

Keyword(s):

Calcium Hydroxide ◽

Cellular Response ◽

Wistar Rats ◽

Inflammatory Cells ◽

Wistar Rat ◽

Control Group ◽

Pulp Tissue ◽

Pulp Capping ◽

Macrophage Cells ◽

Combined Application

Background: Cellular response of dental pulp to existing lesions, caused by infiltration of inflammatory cells that migrate from blood vessels to the site of injury. Macrophages are the cells that most appear when inflammation occurs. Treatment for maintaining pulp tissue vitality is called pulp capping. Calcium hydroxide as a pulp capping material has the ability to trigger the growth of dentin bridges or remineralization, but calcium hydroxide can induce migration and proliferation of inflammatory cells. Currently the field of dentistry is developing propolis as an alternative pulp capping material. That is because propolis has anti-inflammatory properties. Objective: To analyze the effect of the combination of calcium hydroxide-propolis on the number of macrophage cells in the teeth of wistar rats with pulp perforation. Method: This study used 30 samples of Wistar rats which were preparated until perforation and then divided into 3 groups. The first group continued with filling with cention, the second group continued with application of calcium hydroxide and filled with cention, and the third group continued with the application of combination of calcium hydroxide and propolis and then being filledwithcention. Macrophage cell is calculated histopathologically by using compound light microscope on the 3rd day with 400x magnification. Results: The Kruskal-Wallis test results showed significant differences in macrophages after the combination of calcium hydroxide and propolis (p = 0,000). The combined application of calcium hydroxide and propolis showed higher macrophages than the application of calcium hydroxide and the control group. Conclusion: Application of calcium hydroxide - propolis combination was proven increase the number of macrophage cells in Wistar Rats (Rattus Norvegicus) with pulp perforation

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Inflammatory cellular response to mechanical ventilation in elastase-induced experimental emphysema: role of pre-existing alveolar macrophages infiltration

10.1101/205989 ◽

2017 ◽

Author(s):

Anahita Rouze ◽

Guillaume Voiriot ◽

Elise Guivarch ◽

Françoise Roux ◽

Jeanne Tran Van Nhieu ◽

...

Keyword(s):

Mechanical Ventilation ◽

Alveolar Macrophages ◽

Pulmonary Emphysema ◽

Lung Inflammation ◽

Cellular Response ◽

Invasive Mechanical Ventilation ◽

Inflammatory Cells ◽

Chord Length ◽

Lung Mechanics ◽

Chronic Obstructive

ABSTRACTBackgroundAn excessive pulmonary inflammatory response could explain the poor prognosis of chronic obstructive pulmonary disease (COPD) patients submitted to invasive mechanical ventilation. The aim of this study was to evaluate the response to normal tidal volume (Vt) mechanical ventilation in a murine model of pulmonary emphysema, which represents the alveolar component of COPD. In this model, two time points associated with different levels of lung inflammation but similar lung destruction, were analyzed.MethodsC57BL/6 mice received a tracheal instillation of 5 IU of porcine pancreatic elastase (Elastase mice) or the same volume of saline (Saline mice). Fourteen (D14) and 21 (D21) days after instillation, mice were anesthetized, intubated, and either mechanically ventilated (MV) with a normal Vt (8 mL/kg) or maintained on spontaneous ventilation (SV) during two hours. We analyzed respiratory mechanics, emphysema degree (mean chord length by lung histological analysis), and lung inflammation (bronchoalveolar lavage (BAL) cellularity, proportion and activation of total lung inflammatory cells by flow cytometry).ResultsAs compared with Saline mice, Elastase mice showed a similarly increased mean chord length and pulmonary compliance at D14 and D21, while BAL cellularity was comparable between groups. Lung mechanics was similarly altered during mechanical ventilation in Elastase and Saline mice. Activated alveolar macrophages CD11bmid were present in lung parenchyma in both Elastase SV mice and Elastase MV mice at D14 but were absent at D21 and in Saline mice, indicating an inflammatory state with elastase at D14 only. At D14, Elastase MV mice showed a significant increase in percentage of neutrophils concomitant with a decrease in percentage of alveolar macrophages in total lung, as compared with Elastase SV mice. Furthermore, alveolar macrophages of Elastase MV mice at D14 overexpressed Gr1, and monocytes showed a trend to overexpression of CD62L, compared with Elastase SV mice.ConclusionsIn an elastase-induced model of pulmonary emphysema, normal Vt mechanical ventilation produced an increase in the proportion of pulmonary neutrophils, and an activation of alveolar macrophages and pulmonary monocytes. This response was observed only when the emphysema model showed an underlying inflammation (D14), reflected by the presence of activated alveolar macrophages CD11bmid.

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Ion channels in schwann and glial cells

Trends in Neurosciences ◽

10.1016/0166-2236(85)90144-4 ◽

1985 ◽

Vol 8 ◽

pp. 411-415 ◽

Cited By ~ 61

Author(s):

P.T.A. Gray ◽

J.M. Ritchie

Keyword(s):

Ion Channels ◽

Glial Cells

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Control of genome stability by Slx protein complexes

Biochemical Society Transactions ◽

10.1042/bst0370495 ◽

2009 ◽

Vol 37 (3) ◽

pp. 495-510 ◽

Cited By ~ 26

Author(s):

John Rouse

Keyword(s):

Dna Damage ◽

Dna Replication ◽

Protein Interactions ◽

Cellular Response ◽

Genome Stability ◽

Molecular Mechanisms ◽

Excision Repair ◽

Protein Complexes ◽

Alkylating Agents ◽

Strand Break

The six Saccharomyces cerevisiae SLX genes were identified in a screen for factors required for the viability of cells lacking Sgs1, a member of the RecQ helicase family involved in processing stalled replisomes and in the maintenance of genome stability. The six SLX gene products form three distinct heterodimeric complexes, and all three have catalytic activity. Slx3–Slx2 (also known as Mus81–Mms4) and Slx1–Slx4 are both heterodimeric endonucleases with a marked specificity for branched replication fork-like DNA species, whereas Slx5–Slx8 is a SUMO (small ubiquitin-related modifier)-targeted E3 ubiquitin ligase. All three complexes play important, but distinct, roles in different aspects of the cellular response to DNA damage and perturbed DNA replication. Slx4 interacts physically not only with Slx1, but also with Rad1–Rad10 [XPF (xeroderma pigmentosum complementation group F)–ERCC1 (excision repair cross-complementing 1) in humans], another structure-specific endonuclease that participates in the repair of UV-induced DNA damage and in a subpathway of recombinational DNA DSB (double-strand break) repair. Curiously, Slx4 is essential for repair of DSBs by Rad1–Rad10, but is not required for repair of UV damage. Slx4 also promotes cellular resistance to DNA-alkylating agents that block the progression of replisomes during DNA replication, by facilitating the error-free mode of lesion bypass. This does not require Slx1 or Rad1–Rad10, and so Slx4 has several distinct roles in protecting genome stability. In the present article, I provide an overview of our current understanding of the cellular roles of the Slx proteins, paying particular attention to the advances that have been made in understanding the cellular roles of Slx4. In particular, protein–protein interactions and underlying molecular mechanisms are discussed and I draw attention to the many questions that have yet to be answered.

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Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for immune-related molecules by central nervous system mixed glial cell cultures

Multiple Sclerosis Journal ◽

10.1191/135248506ms1251oa ◽

2006 ◽

Vol 12 (2) ◽

pp. 149-168 ◽

Cited By ~ 24

Author(s):

R P Lisak ◽

J A Benjamins ◽

B Bealmear ◽

B Yao ◽

S Land ◽

...

Keyword(s):

Gene Expression ◽

Central Nervous System ◽

Nervous System ◽

Glial Cells ◽

Gene Array ◽

Inflammatory Cells ◽

Early Gene ◽

Th2 Cytokines ◽

Early Gene Expression ◽

Chip Technology

Cytokines secreted within the central nervous system (CNS) are important in the development of multiple sclerosis (MS) lesions. The balance between Th1, monocyte/macrophage (M/M) and Th2 cytokines in the CNS may be pivotal in determining the outcome of lesion development. We examined the effects of mixtures of cytokines on gene expression by CNS glial cells, as mixtures of cytokines are present in MS lesions, which in turn contain mixtures of glial cells. In this initial analysis by gene array, we examined changes at 6 hours to identify early changes in gene expression that represent primary responses to the cytokines. Rat glial cells were incubated with mixtures of Th1, M/M and Th2 cytokines for 6 hours and examined for changes in early gene expression employing microarray gene chip technology. A minimum of 814 genes were differentially regulated by one or more of the cytokine mixtures in comparison to controls, including changes in expression in a large number of genes for immune system-related proteins. Expression of the proteins for these genes likely influences development and inhibition of MS lesions as well as protective and regenerative processes. Analysing gene expression for the effects of various combinations of exogenous cytokines on glial cells in the absence of the confounding effects of inflammatory cells themselves should increase our understanding of cytokine-induced pathways in the CNS.

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