Epigenetic upregulation of CCL2 and CCL3 via histone modifications in infiltrating macrophages after peripheral nerve injury

Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro; Kishioka, Shiroh

doi:10.1016/j.cyto.2013.09.019

Cited by 77 publications

(59 citation statements)

References 39 publications

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“…The enhanced presence of CCL3 can also explain the immediate analgesic effects, independent from an anti-inflammatory action, evoked by the administration of the CCR1 antagonist J113863 in carrageenan-and CFA-inflamed mice. These results add new insights to the previously reported information related to the involvement of CCR1 in neuropathic [7,11,12,35] or neoplastic [10] pain. The possibility of inhibiting inflammatory pain following the acute administration of a CCR1 antagonist seems particularly interesting considering that CCR1 antagonists are already being tested in clinical trials, and that a CCR1 antagonist has been shown to improve rheumatoid arthritis without inducing remarkable adverse reactions [21].…”

Section: Discussionsupporting

confidence: 60%

Involvement of CC Chemokine Receptor 1 and CCL3 in Acute and Chronic Inflammatory Pain in Mice

Llorián-Salvador

González-Rodríguez

Lastra

et al. 2016

Basic Clin Pharma Tox

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Chemokines are chemotactic cytokines whose involvement in nociceptive processing is being increasingly recognized. Based on the previous description of the involvement of CC chemokine receptor type 1 (CCR1) in pathological pain, we have assessed the participation of CCR1 and its endogenous ligands CCL3 and CCL5 in hyperalgesia and allodynia in mice after acute inflammation with carrageenan and chronic inflammation with complete Freund's adjuvant (CFA). The subcutaneous administration of the CCR1 antagonist J113863 (3-30 mg/kg; 30 min. before) dose dependently inhibited carrageenan-and CFA-evoked thermal hyperalgesia and mechanical allodynia produced by CFA, but not by carrageenan. The maximal dose of J113863 did not modify the increase in paw thickness induced by carrageenan or CFA. An almost ten times augmentation of CCL3 levels was detected by ELISA assays in both carrageenan and CFA paws, but not in spinal cords of inflamed mice, whereas CCL5 concentrations remained unaltered. Accordingly, a marked increase of CCL3 mRNA expression was observed in inflamed paws, with CCL3 protein detected in neutrophils and macrophages by immunohistochemical experiments. The intraplantar administration of an anti-CCL3 antibody (0.3-3 lg) blocked thermal hyperalgesia in carrageenan-and CFA-inflamed mice as well as CFA-evoked mechanical allodynia. Our data suggest that the increased concentrations of CCL3 present in inflamed tissues can be involved in acute and chronic inflammatory hyperalgesia as well as in chronic mechanical allodynia, and that these hypernociceptive symptoms can be counteracted by its neutralization with an antibody or by the blockade of CCR1 receptors.Chemokines are chemotactic cytokines involved in inflammatory processes, mainly by favouring immune cell recruitment. Several chemokines activate nociceptive pathways at both peripheral and central level, and this explains their participation in different types of pathological pain [1][2][3][4]. CC chemokine receptor type 1 (CCR1) is expressed in neurons of dorsal root ganglia (DRG) [5,6] as well as in central structures related to pain [7,8]. The stimulation of CCR1 expressed in nociceptors causes Ca 2+ influx and enhances capsaicin responsiveness [6], and the local administration of CCR1 agonists elicits nociceptive behaviours in mice [9,10]. CCR1 is up-regulated in sensory neurons [11] and the spinal cord [7,12] after nerve injury and increased CCR1 mRNA has also been measured in rats 24 hr after receiving carrageenan [13], supporting its involvement in nociceptive processing. Functionally, it has been reported that some types of neuropathic pain can be alleviated by blocking CCR1 expression with siRNA [11], and that the administration of a CCR1 antagonist can prevent some types of murine bone cancer pain [10] and partially reduce writhing responses in mice receiving intraperitoneal acetic acid or mechanical hyperalgesia in inflamed mice [14]. Among the different chemokines able to activate CCR1 [15], CCL3 (MIP-1a, macrophage inflammatory protein-1...

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Section: Discussionsupporting

confidence: 60%

Involvement of CC Chemokine Receptor 1 and CCL3 in Acute and Chronic Inflammatory Pain in Mice

Llorián-Salvador

González-Rodríguez

Lastra

et al. 2016

Basic Clin Pharma Tox

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“…Both in vitro and in vivo studies have shown that these factors are rapidly produced by Schwann cells after peripheral nerve injury, and then function as the chemoattractants for macrophage infiltration [79,80,86,109,121]. Additionally, macrophages infiltrated into injured nerves also express and produce several factors, such as CCL2, TNF-α, IL-1α and IL-1β, thus contributing to further recruitment of monocytes/macrophages [52,109]. These data imply that blockade of these factors would abolish injury-induced macrophage infiltration.…”

Section: Recruitment Of Monocytes/macrophages Into Injury Sitesmentioning

confidence: 96%

“…However, the therapeutic application of IL-10 has been limited, CCL2-CCR2 Sciatic nerve ligation injury upregulates the expression of CCL2-CCR2 signal, which in turn polarizes macrophage to M2 phenotype [52,103,112,117,120] GPR84 Ablation of GPR84 induces macrophage M2 polarization after sciatic nerve ligation injury [82] due to the fact that the in vivo bioactive half-life of IL-10 or its peptide fragments only remains for minutes to hours [98]. Interestingly, Potas et al recently found that implantation of IL-10 conjugated electrospun poly(ε-caprolactone) (PCL) nanofibrous scaffolds in sciatic nerve effectively promotes macrophage M2 polarization up to 14 days [90].…”

Section: Role Of Macrophages In Peripheral Nerve Regenerationmentioning

confidence: 99%

Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury

2015

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The peripheral nervous system (PNS) has remarkable regenerative abilities after injury. Successful PNS regeneration relies on both injured axons and non-neuronal cells, including Schwann cells and immune cells. Macrophages are the most notable immune cells that play key roles in PNS injury and repair. Upon peripheral nerve injury, a large number of macrophages are accumulated at the injury sites, where they not only contribute to Wallerian degeneration, but also are educated by the local microenvironment and polarized to an anti-inflammatory phenotype (M2), thus contributing to axonal regeneration. Significant progress has been made in understanding how macrophages are educated and polarized in the injured microenvironment as well as how they contribute to axonal regeneration. Following the discussion on the main properties of macrophages and their phenotypes, in this review, we will summarize the current knowledge regarding the mechanisms of macrophage infiltration after PNS injury. Moreover, we will discuss the recent findings elucidating how macrophages are polarized to M2 phenotype in the injured PNS microenvironment, as well as the role and underlying mechanisms of macrophages in peripheral nerve injury, Wallerian degeneration and regeneration. Furthermore, we will highlight the potential application by targeting macrophages in treating peripheral nerve injury and peripheral neuropathies.

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“…We have previously shown that epigenetic mechanisms contribute to lung macrophage hyporesponsiveness observed in septic mice, almost certainly contributing to the immune suppression that occurs in both experimental and clinical sepsis (49). Expression of MCP-1/CCL2 in macrophages is also regulated by epigenetic histone modification (50), and KC/CXCL1 and MIP-2/CXCL2 expression in normal human bronchial epithelial cells is regulated by histone post-translational modifications (51). In our study, we found that histone deactylase activity, but not demethyase activity, constitutively regulates LPS-induced KC/CXCL1 expression and contributes to the LPS tolerance response observed.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation of Tolerance to Toll-Like Receptor Ligands in Alveolar Epithelial Cells

Neagos

Standiford

Newstead

et al. 2015

Am J Respir Cell Mol Biol

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To protect the host against exuberant inflammation and injury responses, cells have the ability to become hyporesponsive or "tolerized" to repeated stimulation by microbial and nonmicrobial insults. The lung airspace is constantly exposed to a variety of exogenous and endogenous Toll-like receptor (TLR) ligands, yet the ability of alveolar epithelial cells (AECs) to be tolerized has yet to be examined. We hypothesize that type II AECs will develop a tolerance phenotype upon repeated TLR agonist exposure. To test this hypothesis, primary AECs isolated from the lungs of mice and a murine AEC cell line (MLE-12) were stimulated with either a vehicle control or a TLR ligand for 18 hours, washed, then restimulated with either vehicle or TLR ligand for an additional 6 hours. Tolerance was assessed by measurement of TLR ligand-stimulated chemokine production (monocyte chemoattractant protein

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Epigenetic upregulation of CCL2 and CCL3 via histone modifications in infiltrating macrophages after peripheral nerve injury

Cited by 77 publications

References 39 publications

Involvement of CC Chemokine Receptor 1 and CCL3 in Acute and Chronic Inflammatory Pain in Mice

Involvement of CC Chemokine Receptor 1 and CCL3 in Acute and Chronic Inflammatory Pain in Mice

Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury

Epigenetic Regulation of Tolerance to Toll-Like Receptor Ligands in Alveolar Epithelial Cells

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