c-Src function is necessary and sufficient for triggering microglial cell activation

Glia ◽  
2014 ◽  
Vol 63 (3) ◽  
pp. 497-511 ◽  
Author(s):  
Renato Socodato ◽  
Camila C. Portugal ◽  
Ivan Domith ◽  
Nádia A. Oliveira ◽  
Vivian S. M. Coreixas ◽  
...  
Keyword(s):  
Cell Activation ◽  
Microglial Cell ◽  
Necessary And Sufficient

scholarly journals NK cell activation through the NKG2D ligand MULT-1 is selectively prevented by the glycoprotein encoded by mouse cytomegalovirus gene m145

2005 ◽  
Vol 201 (2) ◽  
pp. 211-220 ◽  
Author(s):  
Astrid Krmpotic ◽  
Milena Hasan ◽  
Andrea Loewendorf ◽  
Tanja Saulig ◽  
Anne Halenius ◽  
...  
Keyword(s):  
Cell Activation ◽  
Nk Cell ◽  
Surface Expression ◽  
Viral Gene ◽  
Nkg2d Ligand ◽  
Mouse Cytomegalovirus ◽  
Mcmv Infection ◽  
Viral Survival ◽  
Necessary And Sufficient

The NK cell–activating receptor NKG2D interacts with three different cellular ligands, all of which are regulated by mouse cytomegalovirus (MCMV). We set out to define the viral gene product regulating murine UL16-binding protein-like transcript (MULT)-1, a newly described NKG2D ligand. We show that MCMV infection strongly induces MULT-1 gene expression, but surface expression of this glycoprotein is nevertheless completely abolished by the virus. Screening a panel of MCMV deletion mutants defined the gene m145 as the viral regulator of MULT-1. The MCMV m145-encoded glycoprotein turned out to be necessary and sufficient to regulate MULT-1 by preventing plasma membrane residence of MULT-1. The importance of MULT-1 in NK cell regulation in vivo was confirmed by the attenuating effect of the m145 deletion that was lifted after NK cell depletion. Our findings underline the significance of escaping MULT-1/NKG2D signaling for viral survival and maintenance.

scholarly journals CD28-B7 interactions allow the induction of CD8+ cytotoxic T lymphocytes in the absence of exogenous help.

1993 ◽  
Vol 177 (6) ◽  
pp. 1791-1796 ◽  
Author(s):  
F A Harding ◽  
J P Allison
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Cells ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Histocompatibility Complex ◽  
Necessary And Sufficient ◽  
Additional Antigen

The activation requirements for the generation of CD8+ cytotoxic T cells (CTL) are poorly understood. Here we demonstrate that in the absence of exogenous help, a CD28-B7 interaction is necessary and sufficient for generation of class I major histocompatibility complex-specific CTL. Costimulation is required only during the inductive phase of the response, and not during the effector phase. Transfection of the CD28 counter receptor, B7, into nonstimulatory P815 cells confers the ability to elicit P815-specific CTL, and this response can be inhibited by anti-CD28 Fab or by the chimeric B7-binding protein CTLA4Ig. Anti-CD28 monoclonal antibody (mAb) can provide a costimulatory signal to CD8+ T cells when the costimulatory capacity of splenic stimulators is destroyed by chemical fixation. CD28-mediated signaling provokes the release of interleukin 2 (IL-2) from the CD8+ CTL precursors, as anti-CD28 mAb could be substituted for by the addition of IL-2, and an anti-IL-2 mAb can block the generation of anti-CD28-induced CTL. CD4+ cells are not involved in the costimulatory response in the systems examined. We conclude that CD8+ T cell activation requires two signals: an antigen-specific signal mediated by the T cell receptor, and an additional antigen nonspecific signal provided via a CD28-B7 interaction.

Neuroinflammation as a possible link between cannabinoids and addiction

2013 ◽  
Vol 26 (6) ◽  
pp. 334-346 ◽  
Author(s):  
Livia C.M. Rodrigues ◽  
Pedro H. Gobira ◽  
Antonio Carlos de Oliveira ◽  
Renan Pelição ◽  
Antonio Lucio Teixeira ◽  
...  
Keyword(s):  
Drug Addiction ◽  
Microglial Activation ◽  
Cell Activation ◽  
Microglial Cell ◽  
Substance Dependence ◽  
Present Review ◽  
Therapeutic Effects ◽  
Neuroprotective Effects ◽  
The Past

ObjectiveSubstance dependence disorder is a chronically relapsing condition characterised by neurobiological changes leading to loss of control in restricting a substance intake, compulsion and withdrawal syndrome. In the past few years, (endo)cannabinoids have been raised as a possible target in the aetiology of drug addiction. On the other hand, although the exact mechanisms of the genesis of addiction remain poorly understood, it is possible that neuroinflammation might also play a role in the pathophysiology of this condition. Studies demonstrated that (endo)cannabinoids act as immunomodulators by inhibiting cytokines production and microglial cell activation. Thus, in the present review, we explore the possible role of neuroinflammation on the therapeutic effects of cannabinoids on drug addiction.MethodsWe conducted an evidence-based review of the literature in order to assess the role of cannabinoids on the neuroinflammatory hypothesis of addiction (terms: addiction, cannabinoids and inflammation). We searched PubMed and BioMedCentral databases up to April 2014 with no date restrictions.ResultsIn all, 165 eligible articles were included in the present review. Existing evidence suggests that disruption in cannabinoid signalling during the drug addiction process leads to microglial activation and neuroinflammation.ConclusionThe literature showed that inflammation and changes in endocannabinod signalling occur in drug abuse; however, it remains uncertain whether these changes are causally or coincidentally associated with addiction. Additional studies, therefore, are needed to elucidate the contribution of neuroinflammation on the behavioural and neuroprotective effects of cannabinoids on drug addiction.

scholarly journals Hormone regulation of microglial cell activation: relevance to multiple sclerosis

2005 ◽  
Vol 48 (2) ◽  
pp. 322-327 ◽  
Author(s):  
Paul D. Drew ◽  
Paul D. Storer ◽  
Jihong Xu ◽  
Janet A. Chavis
Keyword(s):  
Multiple Sclerosis ◽  
Cell Activation ◽  
Microglial Cell ◽  
Hormone Regulation

scholarly journals Signaling of Macrophage Inflammatory Protein (MIP)-3β Facilitates Dengue Virus-Induced Microglial Cell Migration

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 690
Author(s):  
Ming-Kai Jhan ◽  
Ting-Jing Shen ◽  
Po-Chun Tseng ◽  
Yung-Ting Wang ◽  
Chiou-Feng Lin
Keyword(s):  
Cell Migration ◽  
Dengue Virus ◽  
Viral Entry ◽  
Cell Activation ◽  
Microglial Cell ◽  
Inflammatory Protein ◽  
Infected Cells ◽  
Chemotactic Factors ◽  
And Migration ◽  
Macrophage Inflammatory Protein

The infection by dengue virus (DENV) of microglia causes cell activation and migration via a mechanism involving viral entry, RNA release, and Toll-like receptor 3 signaling. In this study, we demonstrated that secreted chemotactic factors present in microglial conditioned medium (MCM) facilitated cell motility in the murine BV2 microglial cells. The pharmacological disruption of lipid rafts/caveolae reduced DENV- and ultraviolet (UV)-inactivated MCM-induced microglial cell migration. An antibody-based cytokine/chemokine array showed an increase in macrophage inflammatory protein (MIP)-3β in MCM produced using DENV-infected cells. The pharmacological inhibition of c-Jun N-terminal kinase (JNK) retarded UV-MCM-induced microglial cell migration. These results demonstrate that secreted MIP-3β and its effect on the JNK signaling pathways mediates DENV-induced BV2 microglial cell migration.

scholarly journals Biphalin, a Dimeric Enkephalin, Alleviates LPS-Induced Activation in Rat Primary Microglial Cultures in Opioid Receptor-Dependent and Receptor-Independent Manners

2017 ◽  
Vol 2017 ◽  
pp. 1-19 ◽  
Author(s):  
Katarzyna Popiolek-Barczyk ◽  
Anna Piotrowska ◽  
Wioletta Makuch ◽  
Joanna Mika
Keyword(s):  
Neuropathic Pain ◽  
Opioid Receptor ◽  
Pain Therapy ◽  
Cell Activation ◽  
Microglial Cell ◽  
Preclinical Model ◽  
No Production ◽  
Dependent Manner ◽  
Analgesic Effects ◽  
Primary Microglial Cell

Neuropathic pain is relatively less responsive to opioids than other types of pain, which is possibly due to a disrupted opioid system partially caused by the profound microglial cell activation that underlines neuroinflammation. We demonstrated that intrathecally injected biphalin, a dimeric enkephalin analog, diminished symptoms of neuropathy in a preclinical model of neuropathic pain in rats (CCI, chronic constriction injury of the sciatic nerve) at day 12 postinjury. Using primary microglial cell cultures, we revealed that biphalin did not influence cell viability but diminished NO production and expression of Iba1 in LPS-stimulated cells. Biphalin also diminished MOP receptor level, as well as pronociceptive mediators (iNOS, IL-1β, and IL-18) in an opioid receptor-dependent manner, and it was correlated with diminished p-NF-κB, p-IκB, p-p38MAPK, and TRIF levels. Biphalin reduced IL-6, IL-10, TNFα, p-STAT3, and p-ERK1/2 and upregulated SOCS3, TLR4, and MyD88; however, this effect was not reversed by naloxone pretreatment. Our study provides evidence that biphalin diminishes neuropathy symptoms, which might be partially related to reduced pronociceptive mediators released by activated microglia. Biphalin may be a putative drug for future pain therapy, especially for the treatment of neuropathic pain, when the lower analgesic effects of morphine are correlated with profound microglial cell activation.

scholarly journals Apamin Suppresses LPS-Induced Neuroinflammatory Responses by Regulating SK Channels and TLR4-Mediated Signaling Pathways

2020 ◽  
Vol 21 (12) ◽  
pp. 4319 ◽  
Author(s):  
Jihyun Park ◽  
Kyung Mi Jang ◽  
Kwan-Kyu Park
Keyword(s):  
Cell Activation ◽  
Microglial Cell ◽  
Vital Role ◽  
Sk Channels ◽  
Neuroinflammatory Response ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Light Chain Enhancer ◽  
Small Conductance

Neuroinflammation plays a vital role in neurodegenerative conditions. Microglia are a key component of the neuroinflammatory response. There is a growing interest in developing drugs to target microglia and thereby control neuroinflammatory processes. Apamin (APM) is a specifically selective antagonist of small conductance calcium-activated potassium (SK) channels. However, its effect on neuroinflammation is largely unknown. We examine the effects of APM on lipopolysaccharide (LPS)-stimulated BV2 and rat primary microglial cells. Regarding the molecular mechanism by which APM significantly inhibits proinflammatory cytokine production and microglial cell activation, we found that APM does so by reducing the expression of phosphorylated CaMKII and toll-like receptor (TLR4). In particular, APM potently suppressed the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/signal transducer and activator of transcription (STAT)3 and phosphorylated mitogen-activated protein kinases (MAPK)-extracellular signal-regulated kinase (ERK). In addition, the correlation of NF-κB/STAT3 and MAPK-ERK in the neuroinflammatory response was verified through inhibitors. The literature and our findings suggest that APM is a promising candidate for an anti-neuroinflammatory agent and can potentially be used for the prevention and treatment of various neurological disorders.

scholarly journals Two Distinct Tyrosine-based Motifs Enable the Inhibitory Receptor FcγRIIB to Cooperatively Recruit the Inositol Phosphatases SHIP1/2 and the Adapters Grb2/Grap

2004 ◽  
Vol 279 (50) ◽  
pp. 51931-51938 ◽  
Author(s):  
Isabelle Isnardi ◽  
Renaud Lesourne ◽  
Pierre Bruhns ◽  
Wolf H. Fridman ◽  
John C. Cambier ◽  
...  
Keyword(s):  
Cell Activation ◽  
Sh2 Domain ◽  
Scaffold Proteins ◽  
Src Homology 2 ◽  
Dependent Cell ◽  
Trimolecular Complex ◽  
Src Homology ◽  
Inositol Phosphatases ◽  
Necessary And Sufficient ◽  
Activation Motif

FcγRIIB are low-affinity receptors for IgG that contain an immunoreceptor tyrosine-based inhibition motif (ITIM) and inhibit immunoreceptor tyrosine-based activation motif (ITAM)-dependent cell activation. When coaggregated with ITAM-bearing receptors, FcγRIIB become tyrosyl-phosphorylated and recruit the Src homology 2 (SH2) domain-containing inositol 5′-phosphatases SHIP1 and SHIP2, which mediate inhibition. The FcγRIIB ITIM was proposed to be necessary and sufficient for recruiting SHIP1/2. We show here that a second tyrosine-containing motif in the intracytoplasmic domain of FcγRIIB is required for SHIP1/2 to be coprecipitated with the receptor. This motif functions as a docking site for the SH2 domain-containing adapters Grb2 and Grap. These adapters interact via their C-terminal SH3 domain with SHIP1/2 to form a stable receptor-phosphatase-adapter trimolecular complex. Both Grb2 and Grap are required for an optimal coprecipitation of SHIP with FcγRIIB, but one adapter is sufficient for the phosphatase to coprecipitate in a detectable manner with the receptors. In addition to facilitating the recruitment of SHIPs, the second tyrosine-based motif may confer upon FcγRIIB the properties of scaffold proteins capable of altering the composition and stability of the signaling complexes generated following receptor engagement.

scholarly journals Taming of macrophage and microglial cell activation by microRNA-124

Cell Research ◽  
2011 ◽  
Vol 21 (2) ◽  
pp. 213-216 ◽  
Author(s):  
Ashley T Conrad ◽  
Bonnie N Dittel
Keyword(s):  
Cell Activation ◽  
Microglial Cell ◽  
Microrna 124
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