&lt;p&gt;Targeting Chemokines and Chemokine Receptors in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis&lt;/p&gt;

Dhaiban, Sarah; Al‐Ani, Mena; Elemam, Noha Mousaad; Maghazachi, Azzam A.

doi:10.2147/jir.s270872

Cited by 38 publications

(27 citation statements)

References 131 publications

(177 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CXCL10 is a chemokine that binds to CXCR3 and thus is a chemo-attractant for activated T cells and natural killer cells 56 . There is evidence its upregulation in MS as well as in EAE and its expression in advance of evidence of T cell invasion in the pre-symptomatic stage would be consistent with its role in helping to initiate subsequent T cell invasion 57 .…”

Section: Discussionmentioning

confidence: 77%

Characterization of microglial transcriptomes in the brain and spinal cord of mice in early and late experimental autoimmune encephalomyelitis using a RiboTag strategy

Acharjee

Gordon

Lee

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Microglia play an important role in the pathogenesis of multiple sclerosis and the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). To more fully understand the role of microglia in EAE we characterized microglial transcriptomes before the onset of motor symptoms (pre-onset) and during symptomatic EAE. We compared the transcriptome in brain, where behavioral changes are initiated, and spinal cord, where damage is revealed as motor and sensory deficits. We used a RiboTag strategy to characterize ribosome-bound mRNA only in microglia without incurring possible transcriptional changes after cell isolation. Brain and spinal cord samples clustered separately at both stages of EAE, indicating regional heterogeneity. Differences in gene expression were observed in the brain and spinal cord of pre-onset and symptomatic animals with most profound effects in the spinal cord of symptomatic animals. Canonical pathway analysis revealed changes in neuroinflammatory pathways, immune functions and enhanced cell division in both pre-onset and symptomatic brain and spinal cord. We also observed a continuum of many pathways at pre-onset stage that continue into the symptomatic stage of EAE. Our results provide additional evidence of regional and temporal heterogeneity in microglial gene expression patterns that may help in understanding mechanisms underlying various symptomology in MS.

show abstract

Section: Discussionmentioning

confidence: 77%

Characterization of microglial transcriptomes in the brain and spinal cord of mice in early and late experimental autoimmune encephalomyelitis using a RiboTag strategy

Acharjee

Gordon

Lee

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Chemokines and their receptors have numerous functions in regulating the immune system, whether in physiological or pathological conditions such as MS. 51–55 CCL3, is involved in the pathophysiology of MS, 55–57 and is expressed within the CNS of EAE mice. 58 We confirmed these findings and observed that Ccl3 mRNA was increased in untreated EAE mice.…”

Section: Discussionmentioning

confidence: 99%

“…59 In our hands, Herceptin therapy reduced Ccl3 mRNA levels in the treated groups when used prophylactically or therapeutically, which could explain the observed reduction of inflammation. Another macrophage-associated chemokine is CCL6, which is released by microglia and macrophages and acts in an autocrine fashion as a strong chemoattractant for macrophages, 60 monocytes, 55 , 61 and T cells. 55 However, to the best of our knowledge, no previous data regarding Ccl6 was reported in EAE.…”

Section: Discussionmentioning

confidence: 99%

“…Another macrophage-associated chemokine is CCL6, which is released by microglia and macrophages and acts in an autocrine fashion as a strong chemoattractant for macrophages, 60 monocytes, 55 , 61 and T cells. 55 However, to the best of our knowledge, no previous data regarding Ccl6 was reported in EAE. Ccl6 mRNA was found to be upregulated in the brains of untreated mice in HCS and was reduced by the administration of Herceptin used in either prophylactic or therapeutic treatment regimen.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Examination of Differentially Expressed Genes in the Brains of Experimental Autoimmune Encephalomyelitis Mice Post Herceptin Treatment

Al‐Ani¹,

Elemam²,

Hachim³

et al. 2021

JIR

Self Cite

View full text Add to dashboard Cite

Objective Herceptin (trastuzumab) is an approved drug for treating HER2 + breast cancer patients, but its use for other diseases is not established. We sought to investigate the effects of Herceptin on ameliorating experimental autoimmune encephalomyelitis (EAE) and to examine its effects on the expression of various genes. Methods We used in-silico analysis of publicly available data, qRT-PCR, and immunohistochemistry (IHC) to determine the expression of HER2 + cells in the brains of EAE mice. IHC was also utilized to determine the anti-inflammatory effects of Herceptin. The ability of Herceptin to alleviate the EAE clinical score was measured in these mice. Bioinformatics analysis of publicly available data and qRT-PCR were performed to investigate the differentially expressed genes that were either up-regulated or down-regulated during the high clinical score (HCS) of the disease. Results We observed that HER2/Erbb2, the receptor for Herceptin is upregulated in the brains of EAE mice when the brains were examined at the HCS stage. Further, we demonstrated that Herceptin ameliorates the EAE disease, increasing re-myelination, reducing brain inflammation, CD3 + T cell accumulation, and HER2 + cells in the brains of these mice. Molecular analysis demonstrated the expression of different genes that were either up-regulated or down-regulated during the HCS of the disease. Our combined bioinformatics and qRT-PCR analyses show increased mRNA expression of Atp6v0d2, C3, C3ar1, Ccl3, Ccl6, Cd74, Clec7a, Cybb, H2-Aa, Hspb1, Lilr4b, Lilrb4a, Mpeg1, Ms4a4a, Ms4a6c, Saa3, Serpina3n and Timp1, at HCS. Except for the mRNA levels of Cd74 and Clec7a which were increased at HCS when Herceptin was used in both prophylactic and therapeutic regimens, the levels of other described mRNAs were reduced. Conclusion These novel findings show that Herceptin ameliorates the clinical score in EAE mice and are the first to investigate in detail the differential gene expression post-treatment with the drug.

show abstract

“…Although the role of CCL2 in the activation of microglia and astrocytes in neuroinflammation is well documented [ 2 , 31 , 32 ], recent studies have shown that PDGFRβ cells (mural cells of blood vessels) are the significant source of CCL2 during early neuroinflammation [ 21 ]. Robust experimental evidence indicates that elevated CCL2 levels induce the recruitment of macrophages, production of cytokines, and direct alteration of the expression of endothelial cell tight-junction proteins to increase blood–brain barrier (BBB) permeability, observed during various pathological processes, such as multiple sclerosis [ 33 , 34 ], stroke [ 35 , 36 ], and Alzheimer’s disease [ 37 , 38 ].…”

Section: Ccl2—possible Effects In the Brainmentioning

confidence: 99%

Targeting the CCL2-CCR2 axis in depressive disorders

Curzytek

Leśkiewicz

2021

Pharmacol. Rep

View full text Add to dashboard Cite

Since affective disorders are considered to be underlain by the immune system malfunction, an important role in their pathophysiology is assigned to the proinflammatory mediators. Recently, chemokines, the group of chemotactic cytokines, have become a focus for basic and clinical scientists in the context of the development and treatment of brain diseases. Among them, chemokine CCL2 and its main receptor CCR2 have become candidate mediators of abnormal brain-immune system dialogue in depression. Besides the chemotactic activity, the CCL2-CCR2 axis is involved in various neurobiological processes, neurogenesis, neurotransmission, neuroinflammation, neurodegeneration, as well as neuroregeneration. Given the range of immunomodulatory possibilities that the CCL2-CCR2 pair can exert on the nervous system, its proinflammatory properties were initially thought to be a major contributor to the development of depressive disorders. However, further research suggests that the malfunctions of the nervous system are rather associated with impaired homeostatic properties manifested by the CCL2-CCR2 dyad dysfunctions. This review aims to present literature data on the action of the CCL2-CCR2 axis in the central nervous system under physiological and pathological conditions, as well as the contribution of this ligand-receptor system to the processes underlying affective disorders. Additionally, this article draws attention to the importance of the CCL2-CRR2 pathway as a potential pharmacological target with antidepressant potential.

show abstract

<p>Targeting Chemokines and Chemokine Receptors in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis</p>

Cited by 38 publications

References 131 publications

Characterization of microglial transcriptomes in the brain and spinal cord of mice in early and late experimental autoimmune encephalomyelitis using a RiboTag strategy

Characterization of microglial transcriptomes in the brain and spinal cord of mice in early and late experimental autoimmune encephalomyelitis using a RiboTag strategy

Molecular Examination of Differentially Expressed Genes in the Brains of Experimental Autoimmune Encephalomyelitis Mice Post Herceptin Treatment

Targeting the CCL2-CCR2 axis in depressive disorders

Contact Info

Product

Resources

About