| RRC ID |
27901
|
| 著者 |
Kiguchi N, Kobayashi Y, Saika F, Kishioka S.
|
| タイトル |
Epigenetic upregulation of CCL2 and CCL3 via histone modifications in infiltrating macrophages after peripheral nerve injury.
|
| ジャーナル |
Cytokine
|
| Abstract |
To gain insight into the epigenetic regulation of CC-chemokine ligand (CCL) 2 and CCL3, key players in the peripheral sensitization leading to neuropathic pain, we examined the relationship between histone H3 modification and the upregulation of these molecules using a mouse model of neuropathic pain after partial sciatic nerve ligation (PSL). We found that circuiting bone marrow (BM)-derived macrophages infiltrated into the injured sciatic nerve (SCN) using enhanced green fluorescent protein chimeric mice. The mRNA levels of CCL2, CCL3 and their receptors (CCR2 and CCR1/CCR5, respectively) were increased in the injured SCN. Chromatin immunoprecipitation assay revealed that levels of lysine 9-acetylated histone H3 (H3K9Ac) and lysine 4-trimethylated H3 (H3K4me(3)) in the promoter regions of the CCL2 and CCL3 genes were increased in the injured SCN after PSL, indicating the enhancement of gene expression. Immunoreactivity for H3K9Ac and H3K4me(3) was localized in the nuclei of infiltrating BM-derived cells and CCL-expressing cells in the injured SCN. We observed H3K9Ac and H3K4me(3) mainly in the nuclei of recruited macrophages on day 7 after PSL. Furthermore, upregulation of CCLs and CCRs were suppressed by histone acetyltransferase inhibitor, anacardic acid. Taken together, our findings demonstrate that CCL2 and CCL3 are upregulated in the injured peripheral nerve through epigenetic histone modification in infiltrating immune cells such as macrophages. These chemokine cascades may subsequently elicit chronic neuroinflammation following nerve injury.
|
| 巻・号 |
64(3)
|
| ページ |
666-72
|
| 公開日 |
2013-12-1
|
| DOI |
10.1016/j.cyto.2013.09.019
|
| PII |
S1043-4666(13)00710-2
|
| PMID |
24135048
|
| MeSH |
Acetylation
Animals
Bone Marrow Transplantation / methods
Chemokine CCL2 / genetics*
Chemokine CCL2 / metabolism
Chemokine CCL3 / genetics*
Chemokine CCL3 / metabolism
Epigenesis, Genetic
Histones / metabolism*
Immunohistochemistry
Lysine / metabolism
Macrophages / metabolism*
Male
Methylation
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Transgenic
Neuralgia / genetics
Neuralgia / metabolism
Neuralgia / physiopathology
Peripheral Nerve Injuries / genetics
Peripheral Nerve Injuries / metabolism
Peripheral Nerve Injuries / physiopathology*
Receptors, CCR1 / genetics
Receptors, CCR1 / metabolism
Receptors, CCR2 / genetics
Receptors, CCR2 / metabolism
Receptors, CCR5 / genetics
Receptors, CCR5 / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sciatic Nerve / injuries
Sciatic Nerve / metabolism
Time Factors
Up-Regulation
|
| IF |
2.952
|
| 引用数 |
40
|
|
WOS 分野
|
IMMUNOLOGY
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC00267 |
