Simvastatin reduces CCL2 expression in monocyte-derived cells by induction of a repressive CCL2 chromatin state

Zanette, Dalila Lucíola; Eggermond, Marja C.J.A. van; Haasnoot, Geert W.; Elsen, Peter J. van den

doi:10.1016/j.humimm.2013.09.016

Cited by 5 publications

(5 citation statements)

References 35 publications

(38 reference statements)

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“…Of these factors, it is interesting that only CCL2 expression is significantly increased in PGRN-silenced macrophages under normoxic conditions. The interaction between CCL2 and CCR2 is one of the most important signaling for the recruitment of mononuclear phagocytes and monocyte-derived cells themselves also secrete CCL2 [ 44 , 45 ]. Thus, the increase in CCL2 in PGRN-deficient macrophages might play a central role in the recruitment of Iba-1 + myeloid cells into the CNV region.…”

Section: Discussionmentioning

confidence: 99%

Progranulin deficiency in Iba-1+ myeloid cells exacerbates choroidal neovascularization by perturbation of lysosomal function and abnormal inflammation

Takahashi

Nakamura

Otsu

et al. 2021

J Neuroinflammation

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Background Age-related macular degeneration (AMD) is the principal cause of permanent blindness among elderly individuals worldwide. Chronic inflammation in the subretinal space is associated with a progression of exudative AMD. Progranulin (PGRN) is a growth factor secreted from myeloid cells and plays an important role in controlling the lysosomal function. A deficiency in PGRN leads to inflammation of the neurons in the central nervous system. The purpose of this study was to investigate the role played by PGRN in the size of the choroidal neovascularization (CNV) in laser-induced CNV mice. Methods CNVs were induced in C57BL/6J mice by laser photocoagulation of the retina. The expression of PGRN and the accumulation of Iba-1+ cells around the sites of the CNVs were determined. Grn−/−, Grn+/−, and Grn+/+ mice with laser-induced CNVs were also studied. To evaluate the effect of macrophages on the inflammation, we used a macrophage cell line (RAW264.7) in which the expression of PGRN was knocked down by RNA interference and peritoneal macrophages derived from Grn−/− and Grn+/+ mice. These cells were incubated under hypoxic conditions (1% O2). Results Iba-1+ myeloid cells migrated and accumulated in the photocoagulation-induced CNV areas, and the CNV lesions secreted high levels of PGRN in Grn+/+ mice. The size of the CNVs was larger in Grn−/− mice than in Grn+/− and Grn+/+ mice. In Grn−/− mice, the number of ocular-infiltrating Iba-1+ cells around the CNV was higher, and these cells produced more VEGF-A than the cells in the Grn+/+ mice. PGRN-silencing of RAW264.7 cells led to abnormal activation of the cells. In addition, hypoxic conditions promoted the production of proangiogenic and proinflammatory cytokines from PGRN-deficient macrophages. Interestingly, the expression level of lysosome-associated proteins and the number of activated lysosomes increased in PGRN-deficient macrophages. Conclusions These findings indicate that PGRN deficiency in Iba-1+ cells activates the lysosomal function that then leads to abnormal inflammation. The aberrant activation of Iba-1+ myeloid cells might contribute to the progression of the CNV and the regulation of these cells might be a novel therapeutic target for exudative AMD.

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Section: Discussionmentioning

confidence: 99%

Progranulin deficiency in Iba-1+ myeloid cells exacerbates choroidal neovascularization by perturbation of lysosomal function and abnormal inflammation

Takahashi

Nakamura

Otsu

et al. 2021

J Neuroinflammation

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“…Another BMP, BMP-2 is also involved in controlling M2 macrophage by the regulation of jumonji domain containing-3 (Jmjd3), a histone 3 Lys27 (H3K27) demethylase [ 106 ]. And lovastatin was shown to inhibit DNMT activity in vitro , resulting in the demethylation of the BMP2 promoter region [ 107 , 108 ]. Some other interplay between DNA methylation and histone modification in the macrophage polarization will be discussed later in this review (see Figure 3 ).…”

Section: Dna Methylationmentioning

confidence: 99%

Promising landscape for regulating macrophage polarization: epigenetic viewpoint

et al. 2017

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Macrophages are critical myeloid cells with the hallmark of phenotypic heterogeneity and functional plasticity. Macrophages phenotypes are commonly described as classically-activated M1 and alternatively-activated M2 macrophages which play an essential role in the tissues homeostasis and diseases pathogenesis. Alternations of macrophage polarization and function states require precise regulation of target-gene expression. Emerging data demonstrate that epigenetic mechanisms and transcriptional factors are becoming increasingly appreciated in the orchestration of macrophage polarization in response to local environmental signals. This review is to focus on the advanced concepts of epigenetics changes involved with the macrophage polarization, including microRNAs, DNA methylation and histone modification, which are responsible for the altered cellular signaling and signature genes expression during M1 or M2 polarization. Eventually, the persistent investigation and understanding of epigenetic mechanisms in tissue macrophage polarization and function will enhance the potential to develop novel therapeutic targets for various diseases.

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“…ChIP was performed as described previously (Kooistra et al, 2010;Zanette et al, 2013) with minor modifications. Formaldehyde (1%, 10 min) was added to 10 6 microglia and crosslinking was stopped by addition of Glycine (125 mM) followed by two PBS washes.…”

Section: Chromatin Immunoprecipitationmentioning

confidence: 99%

Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing

Schaafsma

Zhang

Zomeren

et al. 2015

Brain, Behavior, and Immunity

130

113

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Simvastatin reduces CCL2 expression in monocyte-derived cells by induction of a repressive CCL2 chromatin state

Cited by 5 publications

References 35 publications

Progranulin deficiency in Iba-1+ myeloid cells exacerbates choroidal neovascularization by perturbation of lysosomal function and abnormal inflammation

Progranulin deficiency in Iba-1+ myeloid cells exacerbates choroidal neovascularization by perturbation of lysosomal function and abnormal inflammation

Promising landscape for regulating macrophage polarization: epigenetic viewpoint

Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing

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