Gene expression profile activated by the chemokine CCL5/RANTES in human neuronal cells

Valerio, Alessandra; Ferrario, Marina; Martínez, Fernando O.; Locati, Massimo; Ghisi, Valentina; Bresciani, Laura G.; Mantovani, Alberto; Spano, PierFranco

doi:10.1002/jnr.20250

Cited by 43 publications

(36 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CCL5 also protects mixed cultures of neurons and astrocytes from excitotoxic NMDA-induced apoptosis (Eugenin et al 2003). This agrees with the finding that numerous CCL5-responsive genes in cultured neurons are involved in the regulation of neuronal survival and differentiation (Valerio et al 2004).…”

Section: Ccl3 Ccl4 and Ccl5supporting

confidence: 87%

Chemokines in CNS injury and repair

2012

View full text Add to dashboard Cite

Recruitment of inflammatory cells is known to drive the secondary damage cascades that are common to injuries of the central nervous system (CNS). Cell activation and infiltration to the injury site is orchestrated by changes in the expression of chemokines, the chemoattractive cytokines. Reducing the numbers of recruited inflammatory cells by the blocking of the action of chemokines has turned out be a promising approach to diminish neuroinflammation and to improve tissue preservation and neovascularization. In addition, several chemokines have been shown to be essential for stem/progenitor cell attraction, their survival, differentiation and cytokine production. Thus, chemokines might indirectly participate in remyelination, neovascularization and neuroprotection, which are important prerequisites for CNS repair after trauma. Moreover, CXCL12 promotes neurite outgrowth in the presence of growth inhibitory CNS myelin and enhances axonal sprouting after spinal cord injury (SCI). Here, we review current knowledge about the exciting functions of chemokines in CNS trauma, including SCI, traumatic brain injury and stroke. We identify common principles of chemokine action and discuss the potentials and challenges of therapeutic interventions with chemokines.

show abstract

Section: Ccl3 Ccl4 and Ccl5supporting

confidence: 87%

Chemokines in CNS injury and repair

2012

View full text Add to dashboard Cite

show abstract

“…11 RANTES, indeed, can induce the expression of genes involved in neuronal survival, neurite outgrowth, and synaptogenesis. 16 However, genetic polymorphisms regulating the expression of RANTES or of its receptor, the CCR5, have been associated with MS progression and severity, suggesting that RANTES expression is associated with increased disease severity. 32 Genetic polymorphisms resulting in lower expression of RANTES (i.e.…”

Section: Discussionmentioning

confidence: 99%

RANTES correlates with inflammatory activity and synaptic excitability in multiple sclerosis

et al. 2016

View full text Add to dashboard Cite

Background: Alterations of synaptic transmission induced by inflammatory activity have been linked to the pathogenic mechanisms of multiple sclerosis (MS). Regulated upon activation, normal T-cell expressed, and secreted (RANTES) is a pro-inflammatory chemokine involved in MS pathophysiology, potentially able to regulate glutamate release and plasticity in MS brains, with relevant consequences on the clinical manifestations of the disease. Objective: To assess the role of RANTES in the regulation of cortical excitability. Methods: We explored the association of RANTES levels in the cerebrospinal fluid (CSF) of newly diagnosed MS patients with magnetic resonance imaging (MRI) and laboratory measures of inflammatory activity, as well its role in the control of cortical excitability and plasticity explored by means of transcranial magnetic stimulation (TMS), and in hippocampal mouse slices in vitro. Results: CSF levels of RANTES were remarkably high only in active MS patients and were correlated with the concentrations of interleukin-1β. RANTES levels were associated with TMS measures of cortical synaptic excitability, but not with long-term potentiation (LTP)-like plasticity. Similar findings were obtained in mouse hippocampal slices in vitro, where we observed that RANTES enhanced basal excitatory synaptic transmission with no effect on LTP. Conclusion: RANTES correlates with inflammation and synaptic excitability in MS brains.

show abstract

“…Expression of Oas1a, Isg15, Tnfsf11, Olr1, and Ccl5 are associated with triggering apoptosis in cells (51)(52)(53)(54)(55)(56), and expression of Cxcl10, Ccl2, A2m, and Tnf can contribute to neurotoxicity in other disease models (57)(58)(59)(60)(61)(62). Additionally, others have reported that deletion of Ccl2 (20) or Cxcr3 (the receptor for CXCL10, CXCL9, and CXCL11, which are increased in our model) (46) can increase survival time in mice after scrapie infection, suggesting that signaling through these chemokines and their receptors can lead to damage.…”

Section: Discussionmentioning

confidence: 99%

Prion Infection of Mouse Brain Reveals Multiple New Upregulated Genes Involved in Neuroinflammation or Signal Transduction

Carroll

Striebel

Race

et al. 2015

J Virol

View full text Add to dashboard Cite

Gliosis is often a preclinical pathological finding in neurodegenerative diseases, including prion diseases, but the mechanisms facilitating gliosis and neuronal damage in these diseases are not understood. To expand our knowledge of the neuroinflammatory response in prion diseases, we assessed the expression of key genes and proteins involved in the inflammatory response and signal transduction in mouse brain at various times after scrapie infection. In brains of scrapie-infected mice at pre-and postclinical stages, we identified 15 previously unreported differentially expressed genes related to inflammation or activation of the STAT signal transduction pathway. Levels for the majority of differentially expressed genes increased with time postinfection. In quantitative immunoblotting experiments of STAT proteins, STAT1␣, phosphorylated-STAT1␣ (pSTAT1␣), and pSTAT3 were increased between 94 and 131 days postinfection (p.i.) in brains of mice infected with strain 22L. Furthermore, a select group of STAT-associated genes was increased preclinically during scrapie infection, suggesting early activation of the STAT signal transduction pathway. Comparison of inflammatory markers between mice infected with scrapie strains 22L and RML indicated that the inflammatory responses and gene expression profiles in the brains were strikingly similar, even though these scrapie strains infect different brain regions. The endogenous interleukin-1 receptor antagonist (IL-1Ra), an inflammatory marker, was newly identified as increasing preclinically in our model and therefore might influence scrapie pathogenesis in vivo. However, in IL1Ra-deficient or overexpressor transgenic mice inoculated with scrapie, neither loss nor overexpression of IL-1Ra demonstrated any observable effect on gliosis, protease-resistant prion protein (PrPres) formation, disease tempo, pathology, or expression of the inflammatory genes analyzed. IMPORTANCEPrion infection leads to PrPres deposition, gliosis, and neuroinflammation in the central nervous system before signs of clinical illness. Using a scrapie mouse model of prion disease to assess various time points postinoculation, we identified 15 unreported genes that were increased in the brains of scrapie-infected mice and were associated with inflammation and/or JAK-STAT activation. Comparison of mice infected with two scrapie strains (22L and RML), which have dissimilar neuropathologies, indicated that the inflammatory responses and gene expression profiles in the brains were similar. Genes that increased prior to clinical signs might be involved in controlling scrapie infection or in facilitating damage to host tissues. We tested the possible role of the endogenous IL-1Ra, which was increased at 70 days p.i. In scrapie-infected mice deficient in or overexpressing IL-1Ra, there was no observable effect on gliosis, PrPres formation, disease tempo, pathology, or expression of inflammatory genes analyzed. P rion diseases are infectious progressive neurodegenerative disorders that can affect both h...

show abstract

Gene expression profile activated by the chemokine CCL5/RANTES in human neuronal cells

Cited by 43 publications

References 52 publications

Chemokines in CNS injury and repair

Chemokines in CNS injury and repair

RANTES correlates with inflammatory activity and synaptic excitability in multiple sclerosis

Prion Infection of Mouse Brain Reveals Multiple New Upregulated Genes Involved in Neuroinflammation or Signal Transduction

Contact Info

Product

Resources

About