The Experts below are selected from a list of 51 Experts worldwide ranked by ideXlab platform
Nan-ping Weng - One of the best experts on this subject based on the ideXlab platform.
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MicroRNA-125b modulates inflammatory Chemokine CCL4 expression in immune cells and its reduction causes CCL4 increase with age.
Aging Cell, 2015Co-Authors: Nai-lin Cheng, Xiaochun Chen, Jiewan Kim, Alvin Shi, Cuong Nguyen, Robert P. Wersto, Nan-ping WengAbstract:Chemokines play a pivotal role in regulating the immune response through a tightly controlled expression. Elevated levels of inflammatory Chemokines commonly occur with aging but the mechanism underlying this age-associated change is not fully understood. Here, we report the role of microRNA-125b (miR-125b) in regulating inflammatory CC Chemokine 4 (CCL4) expression in human immune cells and its altered expression with aging. We first analyzed the mRNA level of CCL4 in eight different types of immune cells including CD4 and CD8 T-cell subsets (naive, central and effector memory), B cells and monocytes in blood from both young (≤42 years) and old (≥70 years) adults. We observed that monocytes and naive CD8 T cells expressed higher levels of CCL4 and exhibited an age-related increase in CCL4. We then found the level of miR-125b was inversely correlated with the level of CCL4 in these cells, and the level of miR-125b was reduced in monocytes and naive CD8 T cells of the old compared to the young adults. Knock-down of miR-125b by shRNA in monocytes and naive CD8 T cells led to an increase of CCL4 protein, whereas enhanced miR-125b expression by transfection in naive CD8 T cells resulted in a reduction of the CCL4 mRNA and protein in response to stimulation. Finally, we demonstrated that miR-125b action requires the ‘seed’ sequence in 3′UTR of CCL4. Together these findings demonstrated that miR-125b is a negative regulator of CCL4 and its reduction is partially responsible for the age-related increase of CCL4.
Tsutomu Takahashi - One of the best experts on this subject based on the ideXlab platform.
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methylmercury induces the expression of Chemokine CCL4 via srf activation in c17 2 mouse neural stem cells
Scientific Reports, 2019Co-Authors: Min-seok Kim, Jin-yong Lee, Tsutomu Takahashi, Takashi Toyama, Takayuki Hoshi, Shusuke Kuge, Yasuyuki Fujiwara, Akira NaganumaAbstract:Methylmercury is an environmental pollutant that causes specific and serious damage to the central nervous system. We have previously shown that C-C motif Chemokine ligand 4 (CCL4) protects cultured neural cells from methylmercury toxicity and expression of CCL4 is specifically induced in mouse brain by methylmercury. In this study, we examined the transcriptional regulatory mechanism that induces CCL4 expression by methylmercury using C17.2 mouse neural stem cells. The promoter region of the CCL4 gene was analyzed by a reporter assay, revealing that the region up to 50 bp upstream from the transcription start site was necessary for inducing expression of CCL4 by methylmercury. Nine transcription factors that might bind to this upstream region and be involved in the induction of CCL4 expression by methylmercury were selected, and the induction of CCL4 expression by methylmercury was suppressed by the knockdown of serum response factor (SRF). In addition, the nuclear level of SRF was elevated by methylmercury, and an increase in the amount bound to the CCL4 gene promoter was also observed. Furthermore, we examined the upstream signaling pathway involved in the induction of CCL4 expression by SRF, and confirmed that activation of p38 and ERK, which are part of the MAPK pathway, are involved. These results suggest that methylmercury induces the expression of CCL4 by activating SRF via the p38 and ERK signaling pathway. Our findings are important for elucidating the mechanism involved in the brain-specific induction of CCL4 expression by methylmercury.
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Chemokine CCL4 induced in mouse brain has a protective role against methylmercury toxicity
Toxics, 2018Co-Authors: Min-seok Kim, Tsutomu Takahashi, Akira Naganuma, Miyuki Iwaishimada, Masatake Fujimura, Takashi Toyama, Gi-wook HwangAbstract:Methylmercury (MeHg) is selectively toxic to the central nervous system, but mechanisms related to its toxicity are poorly understood. In the present study, we identified the Chemokine, C-C motif Chemokine Ligand 4 (CCL4), to be selectively upregulated in the brain of MeHg-administered mice. We then investigated the relationship between CCL4 expression and MeHg toxicity using in vivo and in vitro approaches. We confirmed that in C17.2 cells (a mouse neural stem cell line) and the mouse brain, induction of CCL4 expression occurs prior to cytotoxicity caused by MeHg. We also show that the addition of recombinant CCL4 to the culture medium of mouse xprimary neurons attenuated MeHg toxicity, while knockdown of CCL4 in C17.2 cells resulted in higher MeHg sensitivity compared with control cells. These results suggest that CCL4 is a protective factor against MeHg toxicity and that induction of CCL4 expression is not a result of cytotoxicity by MeHg but is a protective response against MeHg exposure.
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Methylmercury induces a brain-specific increase in Chemokine CCL4 expression in mice.
The Journal of toxicological sciences, 2012Co-Authors: Jin-yong Lee, Gi-wook Hwang, Min-seok Kim, Tsutomu Takahashi, Akira NaganumaAbstract:Expression of the Chemokine genes Ccl2, CCL4, Ccl7, Ccl9, and Ccl12 is increased in cerebellum of mice treated with methylmercury. To investigate the effect of methylmercury on other tissues and organs, levels of Chemokine mRNA were investigated in mouse cerebrum, kidney, liver, and spleen. In cerebrum, expression levels of the five Chemokines were significantly increased after methylmercury treatment. In kidney, expression levels of Ccl2, Ccl7, Ccl9, and Ccl12, but not CCL4 were increased. No significant effects were seen on mRNA levels of the Chemokines in liver and spleen. Thus, although methylmercury increases the expression levels of multiple Chemokines in the brain and kidney, expression of CCL4 increases only in the brain. Hence, this phenomenon may be involved in methylmercury toxicity specific to the central nervous system.
Akira Naganuma - One of the best experts on this subject based on the ideXlab platform.
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methylmercury induces the expression of Chemokine CCL4 via srf activation in c17 2 mouse neural stem cells
Scientific Reports, 2019Co-Authors: Min-seok Kim, Jin-yong Lee, Tsutomu Takahashi, Takashi Toyama, Takayuki Hoshi, Shusuke Kuge, Yasuyuki Fujiwara, Akira NaganumaAbstract:Methylmercury is an environmental pollutant that causes specific and serious damage to the central nervous system. We have previously shown that C-C motif Chemokine ligand 4 (CCL4) protects cultured neural cells from methylmercury toxicity and expression of CCL4 is specifically induced in mouse brain by methylmercury. In this study, we examined the transcriptional regulatory mechanism that induces CCL4 expression by methylmercury using C17.2 mouse neural stem cells. The promoter region of the CCL4 gene was analyzed by a reporter assay, revealing that the region up to 50 bp upstream from the transcription start site was necessary for inducing expression of CCL4 by methylmercury. Nine transcription factors that might bind to this upstream region and be involved in the induction of CCL4 expression by methylmercury were selected, and the induction of CCL4 expression by methylmercury was suppressed by the knockdown of serum response factor (SRF). In addition, the nuclear level of SRF was elevated by methylmercury, and an increase in the amount bound to the CCL4 gene promoter was also observed. Furthermore, we examined the upstream signaling pathway involved in the induction of CCL4 expression by SRF, and confirmed that activation of p38 and ERK, which are part of the MAPK pathway, are involved. These results suggest that methylmercury induces the expression of CCL4 by activating SRF via the p38 and ERK signaling pathway. Our findings are important for elucidating the mechanism involved in the brain-specific induction of CCL4 expression by methylmercury.
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Chemokine CCL4 induced in mouse brain has a protective role against methylmercury toxicity
Toxics, 2018Co-Authors: Min-seok Kim, Tsutomu Takahashi, Akira Naganuma, Miyuki Iwaishimada, Masatake Fujimura, Takashi Toyama, Gi-wook HwangAbstract:Methylmercury (MeHg) is selectively toxic to the central nervous system, but mechanisms related to its toxicity are poorly understood. In the present study, we identified the Chemokine, C-C motif Chemokine Ligand 4 (CCL4), to be selectively upregulated in the brain of MeHg-administered mice. We then investigated the relationship between CCL4 expression and MeHg toxicity using in vivo and in vitro approaches. We confirmed that in C17.2 cells (a mouse neural stem cell line) and the mouse brain, induction of CCL4 expression occurs prior to cytotoxicity caused by MeHg. We also show that the addition of recombinant CCL4 to the culture medium of mouse xprimary neurons attenuated MeHg toxicity, while knockdown of CCL4 in C17.2 cells resulted in higher MeHg sensitivity compared with control cells. These results suggest that CCL4 is a protective factor against MeHg toxicity and that induction of CCL4 expression is not a result of cytotoxicity by MeHg but is a protective response against MeHg exposure.
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Methylmercury induces a brain-specific increase in Chemokine CCL4 expression in mice.
The Journal of toxicological sciences, 2012Co-Authors: Jin-yong Lee, Gi-wook Hwang, Min-seok Kim, Tsutomu Takahashi, Akira NaganumaAbstract:Expression of the Chemokine genes Ccl2, CCL4, Ccl7, Ccl9, and Ccl12 is increased in cerebellum of mice treated with methylmercury. To investigate the effect of methylmercury on other tissues and organs, levels of Chemokine mRNA were investigated in mouse cerebrum, kidney, liver, and spleen. In cerebrum, expression levels of the five Chemokines were significantly increased after methylmercury treatment. In kidney, expression levels of Ccl2, Ccl7, Ccl9, and Ccl12, but not CCL4 were increased. No significant effects were seen on mRNA levels of the Chemokines in liver and spleen. Thus, although methylmercury increases the expression levels of multiple Chemokines in the brain and kidney, expression of CCL4 increases only in the brain. Hence, this phenomenon may be involved in methylmercury toxicity specific to the central nervous system.
Nai-lin Cheng - One of the best experts on this subject based on the ideXlab platform.
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MicroRNA-125b modulates inflammatory Chemokine CCL4 expression in immune cells and its reduction causes CCL4 increase with age.
Aging Cell, 2015Co-Authors: Nai-lin Cheng, Xiaochun Chen, Jiewan Kim, Alvin Shi, Cuong Nguyen, Robert P. Wersto, Nan-ping WengAbstract:Chemokines play a pivotal role in regulating the immune response through a tightly controlled expression. Elevated levels of inflammatory Chemokines commonly occur with aging but the mechanism underlying this age-associated change is not fully understood. Here, we report the role of microRNA-125b (miR-125b) in regulating inflammatory CC Chemokine 4 (CCL4) expression in human immune cells and its altered expression with aging. We first analyzed the mRNA level of CCL4 in eight different types of immune cells including CD4 and CD8 T-cell subsets (naive, central and effector memory), B cells and monocytes in blood from both young (≤42 years) and old (≥70 years) adults. We observed that monocytes and naive CD8 T cells expressed higher levels of CCL4 and exhibited an age-related increase in CCL4. We then found the level of miR-125b was inversely correlated with the level of CCL4 in these cells, and the level of miR-125b was reduced in monocytes and naive CD8 T cells of the old compared to the young adults. Knock-down of miR-125b by shRNA in monocytes and naive CD8 T cells led to an increase of CCL4 protein, whereas enhanced miR-125b expression by transfection in naive CD8 T cells resulted in a reduction of the CCL4 mRNA and protein in response to stimulation. Finally, we demonstrated that miR-125b action requires the ‘seed’ sequence in 3′UTR of CCL4. Together these findings demonstrated that miR-125b is a negative regulator of CCL4 and its reduction is partially responsible for the age-related increase of CCL4.
Min-seok Kim - One of the best experts on this subject based on the ideXlab platform.
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methylmercury induces the expression of Chemokine CCL4 via srf activation in c17 2 mouse neural stem cells
Scientific Reports, 2019Co-Authors: Min-seok Kim, Jin-yong Lee, Tsutomu Takahashi, Takashi Toyama, Takayuki Hoshi, Shusuke Kuge, Yasuyuki Fujiwara, Akira NaganumaAbstract:Methylmercury is an environmental pollutant that causes specific and serious damage to the central nervous system. We have previously shown that C-C motif Chemokine ligand 4 (CCL4) protects cultured neural cells from methylmercury toxicity and expression of CCL4 is specifically induced in mouse brain by methylmercury. In this study, we examined the transcriptional regulatory mechanism that induces CCL4 expression by methylmercury using C17.2 mouse neural stem cells. The promoter region of the CCL4 gene was analyzed by a reporter assay, revealing that the region up to 50 bp upstream from the transcription start site was necessary for inducing expression of CCL4 by methylmercury. Nine transcription factors that might bind to this upstream region and be involved in the induction of CCL4 expression by methylmercury were selected, and the induction of CCL4 expression by methylmercury was suppressed by the knockdown of serum response factor (SRF). In addition, the nuclear level of SRF was elevated by methylmercury, and an increase in the amount bound to the CCL4 gene promoter was also observed. Furthermore, we examined the upstream signaling pathway involved in the induction of CCL4 expression by SRF, and confirmed that activation of p38 and ERK, which are part of the MAPK pathway, are involved. These results suggest that methylmercury induces the expression of CCL4 by activating SRF via the p38 and ERK signaling pathway. Our findings are important for elucidating the mechanism involved in the brain-specific induction of CCL4 expression by methylmercury.
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Chemokine CCL4 induced in mouse brain has a protective role against methylmercury toxicity
Toxics, 2018Co-Authors: Min-seok Kim, Tsutomu Takahashi, Akira Naganuma, Miyuki Iwaishimada, Masatake Fujimura, Takashi Toyama, Gi-wook HwangAbstract:Methylmercury (MeHg) is selectively toxic to the central nervous system, but mechanisms related to its toxicity are poorly understood. In the present study, we identified the Chemokine, C-C motif Chemokine Ligand 4 (CCL4), to be selectively upregulated in the brain of MeHg-administered mice. We then investigated the relationship between CCL4 expression and MeHg toxicity using in vivo and in vitro approaches. We confirmed that in C17.2 cells (a mouse neural stem cell line) and the mouse brain, induction of CCL4 expression occurs prior to cytotoxicity caused by MeHg. We also show that the addition of recombinant CCL4 to the culture medium of mouse xprimary neurons attenuated MeHg toxicity, while knockdown of CCL4 in C17.2 cells resulted in higher MeHg sensitivity compared with control cells. These results suggest that CCL4 is a protective factor against MeHg toxicity and that induction of CCL4 expression is not a result of cytotoxicity by MeHg but is a protective response against MeHg exposure.
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Methylmercury induces a brain-specific increase in Chemokine CCL4 expression in mice.
The Journal of toxicological sciences, 2012Co-Authors: Jin-yong Lee, Gi-wook Hwang, Min-seok Kim, Tsutomu Takahashi, Akira NaganumaAbstract:Expression of the Chemokine genes Ccl2, CCL4, Ccl7, Ccl9, and Ccl12 is increased in cerebellum of mice treated with methylmercury. To investigate the effect of methylmercury on other tissues and organs, levels of Chemokine mRNA were investigated in mouse cerebrum, kidney, liver, and spleen. In cerebrum, expression levels of the five Chemokines were significantly increased after methylmercury treatment. In kidney, expression levels of Ccl2, Ccl7, Ccl9, and Ccl12, but not CCL4 were increased. No significant effects were seen on mRNA levels of the Chemokines in liver and spleen. Thus, although methylmercury increases the expression levels of multiple Chemokines in the brain and kidney, expression of CCL4 increases only in the brain. Hence, this phenomenon may be involved in methylmercury toxicity specific to the central nervous system.