Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Publication

Promoted Interaction of C/EBPα with Demethylated Cxcr3 Gene Promoter Contributes to Neuropathic Pain in Mice.

The Journal of neuroscience : the official journal of the Society for Neuroscience | 2017

DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and how it contributes to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased Cxcr3 mRNA and protein expression in the neurons of the spinal cord. Meanwhile, the CpG (5'-cytosine-phosphate-guanine-3') island in the Cxcr3 gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased. SNL also increased the binding of CCAAT (cytidine-cytidine-adenosine-adenosine-thymidine)/enhancer binding protein α (C/EBPα) with Cxcr3 promoter and decreased the binding of DNMT3b with Cxcr3 promoter in the spinal cord. C/EBPα expression was increased in spinal neurons after SNL, and inhibition of C/EBPα by intrathecal small interfering RNA attenuated SNL-induced pain hypersensitivity and reduced Cxcr3 expression. Furthermore, SNL-induced mechanical allodynia and heat hyperalgesia were markedly reduced in Cxcr3-/- mice. Spinal inhibition of Cxcr3 by shRNA or CXCR3 antagonist also attenuated established neuropathic pain. Moreover, CXCL10, the ligand of CXCR3, was increased in spinal neurons and astrocytes after SNL. Superfusing spinal cord slices with CXCL10 enhanced spontaneous EPSCs and potentiated NMDA-induced and AMPA-induced currents of lamina II neurons. Finally, intrathecal injection of CXCL10 induced CXCR3-dependent pain hypersensitivity in naive mice. Collectively, our results demonstrated that CXCR3, increased by DNA demethylation and the enhanced interaction with C/EBPα, can be activated by CXCL10 to facilitate excitatory synaptic transmission and contribute to the maintenance of neuropathic pain.

Pubmed ID: 28100749 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

None found

Antibodies used in this publication

Associated grants

None

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.

p44/42 MAP kinase (phosphorylated Erk1/2) (antibody)

RRID:AB_331646

This polyclonal targets Erk1/2

View all literature mentions

Anti Iba1, Rabbit antibody (antibody)

RRID:AB_839504

This polyclonal targets Iba1

View all literature mentions

Anti-NeuN (antibody)

RRID:AB_2298772

This monoclonal targets NeuN

View all literature mentions

Human CCL20/MIP-3 alpha MAb (Clone 67310) (antibody)

RRID:AB_2275415

This monoclonal targets Human CCL20/MIP-3 alpha MAb (Clone 67310)

View all literature mentions

Goat Anti-Mouse Cxcl10 / ip-10 / crg-2 Polyclonal antibody, Unconjugated (antibody)

RRID:AB_2292487

This polyclonal targets Mouse CXCL10 / IP-10 / CRG-2

View all literature mentions

NK-1R (L-15) (antibody)

RRID:AB_2255736

This polyclonal targets TACR1

View all literature mentions

Anti-Glyceraldehyde-3-Phosphate Dehydrogenase Antibody, clone 6C5 (antibody)

RRID:AB_2107445

This monoclonal targets Glyceraldehyde-3-PDH (GAPDH)

View all literature mentions

C/EBP alpha (14AA) (antibody)

RRID:AB_631233

This monoclonal targets C/EBP alpha (14AA)

View all literature mentions

Rabbit Anti-Histone H3 XP??? (ChIP Formulated) Monoclonal Antibody, Unconjugated, Clone D2B12 (antibody)

RRID:AB_1904005

This monoclonal targets Histone H3

View all literature mentions

MOUSE ANTI RAT CD11b (antibody)

RRID:AB_566455

This monoclonal targets MOUSE ANTI RAT CD11b

View all literature mentions

Dnmt3b (T-16) (antibody)

RRID:AB_2094128

This polyclonal targets Dnmt3b (T-16)

View all literature mentions

Mouse Anti-Dnmt3b Monoclonal Antibody, Unconjugated, Clone 52A1018 (antibody)

RRID:AB_300494

This monoclonal targets Dnmt3b

View all literature mentions

ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

View all literature mentions