CCL2 disrupts the adherens junction: implications for neuroinflammation

Roberts, Toni K.; Eugenín, Eliseo A.; Lopez, Lillie; Romero, Ignacio A.; Weksler, Babette B.; Couraud, Pierre Olivier; Berman, Joan W.

doi:10.1038/labinvest.2012.80

Cited by 90 publications

(72 citation statements)

References 111 publications

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“…Chemokines also have an effect on BBB disruption, as demonstrated for MCP-1 (CCL2) during HIV-1 infection, where MCP-1 disrupts adherens junctions and transiently opens the endothelial cell barrier (53). Chemokines also affect BBB integrity by enhancing migration of immune cells to the infected brain areas.…”

Section: Discussionmentioning

confidence: 99%

A Protective Role for Interleukin-1 Signaling during Mouse Adenovirus Type 1-Induced Encephalitis

Castro-Jorge

Pretto

Smith

et al. 2017

J Virol

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Interleukin-1␤ (IL-1␤), an inflammatory cytokine and IL-1 receptor ligand, has diverse activities in the brain. We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor (Il1r1 Ϫ/Ϫ mice). Il1r1 Ϫ/Ϫ mice demonstrated reduced survival, greater disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokine and chemokine levels than control C57BL/6J mice. We also examined infections of mice defective in IL-1␤ production (Pycard Ϫ/Ϫ mice) and mice defective in trafficking of Toll-like receptors to the endosome (Unc93b1 Ϫ/Ϫ mice). Pycard Ϫ/Ϫ and Unc93b1 Ϫ/Ϫ mice showed lower survival (similar to Il1r1 Ϫ/Ϫ mice) than control mice but, unlike Il1r1 Ϫ/Ϫ mice, did not have increased brain viral loads or BBB disruption. Based on the brain cytokine levels, MAV-1-infected Unc93b1 Ϫ/Ϫ mice had a very different inflammatory profile from infected Il1r1 Ϫ/Ϫ and Pycard Ϫ/Ϫ mice. Histological examination demonstrated pathological findings consistent with encephalitis in control and knockout mice; however, intranuclear viral inclusions were seen only in Il1r1 Ϫ/Ϫ mice. A time course of infection of control and Il1r1 Ϫ/Ϫ mice evaluating the kinetics of viral replication and cytokine production revealed differences between the mouse strains primarily at 7 to 8 days after infection, when mice began succumbing to MAV-1 infection. In the absence of IL-1 signaling, we noted an increase in the transcription of type I interferon (IFN)-stimulated genes. Together, these results indicate that IL-1 signaling is important during MAV-1 infection and suggest that, in its absence, increased IFN-␤ signaling may result in increased neuroinflammation. IMPORTANCEThe investigation of encephalitis pathogenesis produced by different viruses is needed to characterize virus and host-specific factors that contribute to disease. MAV-1 produces viral encephalitis in its natural host, providing a good model for studying factors involved in encephalitis development. We investigated the role of IL-1 signaling during MAV-1-induced encephalitis. Unexpectedly, the lack of IL-1 signaling increased the mortality and inflammation in mice infected with MAV-1. Also, there was an increase in the transcription of type I IFN-stimulated genes that correlated with the observed increased mortality and inflammation. The findings highlight the complex nature of encephalitis and suggests that IL-1 has a protective effect for the development of MAV-1-induced encephalitis.

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Section: Discussionmentioning

confidence: 99%

A Protective Role for Interleukin-1 Signaling during Mouse Adenovirus Type 1-Induced Encephalitis

Castro-Jorge

Pretto

Smith

et al. 2017

J Virol

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“…It has been shown that CCL2 expression is induced by increased levels of b-amyloid, and this can in turn disrupt the blood-brain barrier and facilitate recruitment of leukocytes into the CNS. 43 In mouse models of Alzheimer's disease, monocytes have been showed to migrate from the bone marrow and infiltrate into brain in a CCR2-dependent manner, and then differentiate into microglia or macrophages. There is growing evidence that CCR2 þ cells may play protective rather than detrimental roles in Alzheimer's disease.…”

Section: Evidence For a Role Of Ccr2 In Central Nervous System Diseasesmentioning

confidence: 99%

Role of CCR2 in Inflammatory Conditions of the Central Nervous System

Chu

Arumugam

Gelderblom

et al. 2014

J Cereb Blood Flow Metab

136

106

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CC chemokine receptor 2 (CCR2) plays important roles in extravasation and transmigration of monocytes under inflammatory conditions. CCR2 and its ligands have been extensively studied in a range of inflammatory diseases in the central nervous system (CNS), including multiple sclerosis, Alzheimer's disease and ischemic stroke. This brief review summarizes our current understanding of the physiologic and pathologic roles of CCR2, focusing on its involvement in CNS inflammatory diseases. There appears to be a rationale for exploring therapies involving CCR2 inhibition in multiple sclerosis and ischemic stroke, but there is also evidence for immunomodulatory and protective effects of CCR2 activity during CNS inflammation. The critical balance between protective and detrimental roles of CCR2-dependent recruitment of leukocytes must therefore be carefully examined to guide safe and effective development of any therapies involving CCR2 modulation.

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“…Thus, CCL2 increases the ability of endothelium to recruit leukocytes into CNS and disrupt the BBB. CCL2 increase in CNS and cerebrospinal fluid has been promoted as a marker of damage to BBB in patients with a neuroinflammatory background [133].…”

Section: Advances In Diagnosis Of Cns Involvement In Leukemiamentioning

confidence: 99%

Central nervous system niche involvement in the leukemia

et al. 2015

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Central nervous system (CNS) impairment is commonly involved in leukemia, as it can be observed upon onset or relapse of the disease. It is associated with poor prognosis and is a challenging clinical problem. The objective of this paper was to provide a characterization of the CNS niche in leukemia, to elucidate the culprits of CNS involvement, including diagnostic micro RNAs (miRs) and early leukemia prognosis. CNS niche is a proper location for homing of leukemic stem cells, thus representing a candidate target in the treatment of leukemia. Recent advances in the study of leukemia hallmarks have enlightened miRs as novel biomarkers for diagnosis and detection of CNS involvement in leukemia, thus providing the opportunity to develop novel therapeutic approaches. Given the importance of prognosis and early diagnosis of CNS involvement in leukemias as well as the severe side effects of current treatments, diagnostic and therapeutic approaches should focus on identification and inhibition of the factors contributing to CNS involvement, including CXCR3, P-selectin glycoprotein ligand-1 and MCP1. MiRs such as miR-221 and miR-222 are emerging as potential tools for an innovative non-invasive therapy of CNS in leukemia affected patients.

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CCL2 disrupts the adherens junction: implications for neuroinflammation

Cited by 90 publications

References 111 publications

A Protective Role for Interleukin-1 Signaling during Mouse Adenovirus Type 1-Induced Encephalitis

A Protective Role for Interleukin-1 Signaling during Mouse Adenovirus Type 1-Induced Encephalitis

Role of CCR2 in Inflammatory Conditions of the Central Nervous System

Central nervous system niche involvement in the leukemia

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