The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
Yoshiro Maru - One of the best experts on this subject based on the ideXlab platform.
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the s100a8 serum amyloid a3 tlr4 paracrine cascade establishes a pre metastatic phase
Nature Cell Biology, 2008Co-Authors: Sachie Hiratsuka, Hiroyuki Aburatani, Akira Watanabe, Yoshiko Sakurai, Sachiko Akashitakamura, Sachie Ishibashi, Kensuke Miyake, Masabumi Shibuya, Shizuo Akira, Yoshiro MaruAbstract:The production of Chemoattractants in the pre-metastatic lung can be induced by distant primary tumours. The Chemoattractants S100A8 and S100A9 induce serum amyloid A3 and TLR4 activation and cause an inflammation-like state that facilitates metastasis. A large number of macrophages and haematopoietic progenitor cells accumulate in pre-metastatic lungs1,2 in which Chemoattractants, such as S100A8 and S100A9, are produced by distant primary tumours serving as metastatic soil3. The exact mechanism by which these Chemoattractants elicit cell accumulation is not known. Here, we show that serum amyloid A (SAA) 3, which is induced in pre-metastatic lungs by S100A8 and S100A9, has a role in the accumulation of myeloid cells and acts as a positive-feedback regulator for chemoattractant secretion. We also show that in lung endothelial cells and macrophages, Toll-like receptor (TLR) 4 acts as a functional receptor for SAA3 in the pre-metastatic phase. In our study, SAA3 stimulated NF-κB signalling in a TLR4-dependent manner and facilitated metastasis. This inflammation-like state accelerated the migration of primary tumour cells to lung tissues, but this was suppressed by the inhibition of either TLR4 or SAA3. Thus, blocking SAA3–TLR4 function in the pre-metastatic phase could prove to be an effective strategy for the prevention of pulmonary metastasis.
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the s100a8 serum amyloid a3 tlr4 paracrine cascade establishes a pre metastatic phase
Nature Cell Biology, 2008Co-Authors: Sachie Hiratsuka, Hiroyuki Aburatani, Akira Watanabe, Yoshiko Sakurai, Sachiko Akashitakamura, Sachie Ishibashi, Kensuke Miyake, Masabumi Shibuya, Shizuo Akira, Yoshiro MaruAbstract:A large number of macrophages and haematopoietic progenitor cells accumulate in pre-metastatic lungs in which Chemoattractants, such as S100A8 and S100A9, are produced by distant primary tumours serving as metastatic soil. The exact mechanism by which these Chemoattractants elicit cell accumulation is not known. Here, we show that serum amyloid A (SAA) 3, which is induced in pre-metastatic lungs by S100A8 and S100A9, has a role in the accumulation of myeloid cells and acts as a positive-feedback regulator for chemoattractant secretion. We also show that in lung endothelial cells and macrophages, Toll-like receptor (TLR) 4 acts as a functional receptor for SAA3 in the pre-metastatic phase. In our study, SAA3 stimulated NF-kappaB signalling in a TLR4-dependent manner and facilitated metastasis. This inflammation-like state accelerated the migration of primary tumour cells to lung tissues, but this was suppressed by the inhibition of either TLR4 or SAA3. Thus, blocking SAA3-TLR4 function in the pre-metastatic phase could prove to be an effective strategy for the prevention of pulmonary metastasis.
Sachie Hiratsuka - One of the best experts on this subject based on the ideXlab platform.
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the s100a8 serum amyloid a3 tlr4 paracrine cascade establishes a pre metastatic phase
Nature Cell Biology, 2008Co-Authors: Sachie Hiratsuka, Hiroyuki Aburatani, Akira Watanabe, Yoshiko Sakurai, Sachiko Akashitakamura, Sachie Ishibashi, Kensuke Miyake, Masabumi Shibuya, Shizuo Akira, Yoshiro MaruAbstract:The production of Chemoattractants in the pre-metastatic lung can be induced by distant primary tumours. The Chemoattractants S100A8 and S100A9 induce serum amyloid A3 and TLR4 activation and cause an inflammation-like state that facilitates metastasis. A large number of macrophages and haematopoietic progenitor cells accumulate in pre-metastatic lungs1,2 in which Chemoattractants, such as S100A8 and S100A9, are produced by distant primary tumours serving as metastatic soil3. The exact mechanism by which these Chemoattractants elicit cell accumulation is not known. Here, we show that serum amyloid A (SAA) 3, which is induced in pre-metastatic lungs by S100A8 and S100A9, has a role in the accumulation of myeloid cells and acts as a positive-feedback regulator for chemoattractant secretion. We also show that in lung endothelial cells and macrophages, Toll-like receptor (TLR) 4 acts as a functional receptor for SAA3 in the pre-metastatic phase. In our study, SAA3 stimulated NF-κB signalling in a TLR4-dependent manner and facilitated metastasis. This inflammation-like state accelerated the migration of primary tumour cells to lung tissues, but this was suppressed by the inhibition of either TLR4 or SAA3. Thus, blocking SAA3–TLR4 function in the pre-metastatic phase could prove to be an effective strategy for the prevention of pulmonary metastasis.
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the s100a8 serum amyloid a3 tlr4 paracrine cascade establishes a pre metastatic phase
Nature Cell Biology, 2008Co-Authors: Sachie Hiratsuka, Hiroyuki Aburatani, Akira Watanabe, Yoshiko Sakurai, Sachiko Akashitakamura, Sachie Ishibashi, Kensuke Miyake, Masabumi Shibuya, Shizuo Akira, Yoshiro MaruAbstract:A large number of macrophages and haematopoietic progenitor cells accumulate in pre-metastatic lungs in which Chemoattractants, such as S100A8 and S100A9, are produced by distant primary tumours serving as metastatic soil. The exact mechanism by which these Chemoattractants elicit cell accumulation is not known. Here, we show that serum amyloid A (SAA) 3, which is induced in pre-metastatic lungs by S100A8 and S100A9, has a role in the accumulation of myeloid cells and acts as a positive-feedback regulator for chemoattractant secretion. We also show that in lung endothelial cells and macrophages, Toll-like receptor (TLR) 4 acts as a functional receptor for SAA3 in the pre-metastatic phase. In our study, SAA3 stimulated NF-kappaB signalling in a TLR4-dependent manner and facilitated metastasis. This inflammation-like state accelerated the migration of primary tumour cells to lung tissues, but this was suppressed by the inhibition of either TLR4 or SAA3. Thus, blocking SAA3-TLR4 function in the pre-metastatic phase could prove to be an effective strategy for the prevention of pulmonary metastasis.
Gary M Bokoch - One of the best experts on this subject based on the ideXlab platform.
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p rex1 is a primary rac2 guanine nucleotide exchange factor in mouse neutrophils
Current Biology, 2005Co-Authors: Xuemei Dong, Zhicheng Mo, Zhong Li, Gary M Bokoch, Dianqing WuAbstract:Summary Leukocyte Chemoattractants regulate many leukocyte functions, including leukocyte chemotaxis, via the Rho family of small GTPases that include RhoA, Cdc42, and Rac [1–4]. Previous work has revealed mechanisms by which Chemoattractants regulate RhoA and Cdc42 in mouse neutrophils [5–8], but the mechanisms for regulation of Rac remain unclear even though Rac is important for neutrophil functions [9–13]. Here, we characterized P-Rex1, a Gβγ and PIP 3 -regulated guanine nucleotide exchange factor that was initially identified as a Rac activator in response to Chemoattractants [14], for its roles in the regulation of Rac activity and neutrophil functions. We generated a mouse line in which the P-Rex1 gene is disrupted and found that P-Rex1 deficiency did not significantly affect Rac1 activation but diminished Rac2 activation in response to a chemoattractant fMLP in mouse neutrophils. This preference for Rac2 may partially result from the apparent higher affinity of P-Rex1 for Rac2 than for Rac1 because P-Rex1 was more readily immunoprecipitated with Rac2 S17N than Rac1 S17N . In addition, P-Rex1 deficiency significantly attenuated fMLP-induced F actin formation and superoxide production without affecting LPS- or PMA-induced production. Furthermore, P-Rex1 deficiency caused a chemotactic defect that is primarily attributed to a reduction in the migration rate rather than directionality.
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P-Rex1 Is a Primary Rac2 Guanine Nucleotide Exchange Factor in Mouse Neutrophils
Current biology : CB, 2005Co-Authors: Xuemei Dong, Gary M Bokoch, Caiying GuoAbstract:Leukocyte Chemoattractants regulate many leukocyte functions, including leukocyte chemotaxis, via the Rho family of small GTPases that include RhoA, Cdc42, and Rac. Previous work has revealed mechanisms by which Chemoattractants regulate RhoA and Cdc42 in mouse neutrophils, but the mechanisms for regulation of Rac remain unclear even though Rac is important for neutrophil functions. Here, we characterized P-Rex1, a Gbetagamma and PIP(3)-regulated guanine nucleotide exchange factor that was initially identified as a Rac activator in response to Chemoattractants, for its roles in the regulation of Rac activity and neutrophil functions. We generated a mouse line in which the P-Rex1 gene is disrupted and found that P-Rex1 deficiency did not significantly affect Rac1 activation but diminished Rac2 activation in response to a chemoattractant fMLP in mouse neutrophils. This preference for Rac2 may partially result from the apparent higher affinity of P-Rex1 for Rac2 than for Rac1 because P-Rex1 was more readily immunoprecipitated with Rac2(S17N) than Rac1(S17N). In addition, P-Rex1 deficiency significantly attenuated fMLP-induced F actin formation and superoxide production without affecting LPS- or PMA-induced production. Furthermore, P-Rex1 deficiency caused a chemotactic defect that is primarily attributed to a reduction in the migration rate rather than directionality.
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g protein coupled chemoattractant receptors regulate lyn tyrosine kinase shc adapter protein signaling complexes
Journal of Biological Chemistry, 1995Co-Authors: Andrzej Ptasznik, Alexis Traynorkaplan, Gary M BokochAbstract:Receptors for Chemoattractants that direct the migration of phagocytic leukocytes to sites of injury/infection also modulate many other leukocyte functions that are critical to the inflammatory response. These chemoattractant receptors, members of the G protein-coupled heptahelical receptor family, have been classically linked to cell activation via phospholipase C, calcium, and protein kinase C. We show here that activation of the N-formyl peptide chemoattractant receptor stimulates an additional protein kinase C-independent pathway through the Src-related tyrosine kinase, Lyn, in human neutrophils. We demonstrate that activation of Lyn is associated with binding to the Shc adapter protein, which becomes phosphorylated on tyrosine residues. This interaction appears to be mediated via the Shc SH2 domain. Complexes of phosphorylated Lyn and Shc with phosphatidylinositol 3-kinase are rapidly formed in stimulated neutrophils, correlating with phosphatidylinositol 1,4,5-trisphosphate formation and cell activation. This signaling pathway involving a Src-related kinase and the Shc adapter protein provides a potential mechanism linking chemoattractant receptors to downstream events involving Rac activation and NADPH oxidase. Regulation of Shc by G protein-coupled receptors may also allow these receptors to modulate the activity of the Ras/mitogen-activated protein kinase cascade.
Xuemei Dong - One of the best experts on this subject based on the ideXlab platform.
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p rex1 is a primary rac2 guanine nucleotide exchange factor in mouse neutrophils
Current Biology, 2005Co-Authors: Xuemei Dong, Zhicheng Mo, Zhong Li, Gary M Bokoch, Dianqing WuAbstract:Summary Leukocyte Chemoattractants regulate many leukocyte functions, including leukocyte chemotaxis, via the Rho family of small GTPases that include RhoA, Cdc42, and Rac [1–4]. Previous work has revealed mechanisms by which Chemoattractants regulate RhoA and Cdc42 in mouse neutrophils [5–8], but the mechanisms for regulation of Rac remain unclear even though Rac is important for neutrophil functions [9–13]. Here, we characterized P-Rex1, a Gβγ and PIP 3 -regulated guanine nucleotide exchange factor that was initially identified as a Rac activator in response to Chemoattractants [14], for its roles in the regulation of Rac activity and neutrophil functions. We generated a mouse line in which the P-Rex1 gene is disrupted and found that P-Rex1 deficiency did not significantly affect Rac1 activation but diminished Rac2 activation in response to a chemoattractant fMLP in mouse neutrophils. This preference for Rac2 may partially result from the apparent higher affinity of P-Rex1 for Rac2 than for Rac1 because P-Rex1 was more readily immunoprecipitated with Rac2 S17N than Rac1 S17N . In addition, P-Rex1 deficiency significantly attenuated fMLP-induced F actin formation and superoxide production without affecting LPS- or PMA-induced production. Furthermore, P-Rex1 deficiency caused a chemotactic defect that is primarily attributed to a reduction in the migration rate rather than directionality.
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P-Rex1 Is a Primary Rac2 Guanine Nucleotide Exchange Factor in Mouse Neutrophils
Current biology : CB, 2005Co-Authors: Xuemei Dong, Gary M Bokoch, Caiying GuoAbstract:Leukocyte Chemoattractants regulate many leukocyte functions, including leukocyte chemotaxis, via the Rho family of small GTPases that include RhoA, Cdc42, and Rac. Previous work has revealed mechanisms by which Chemoattractants regulate RhoA and Cdc42 in mouse neutrophils, but the mechanisms for regulation of Rac remain unclear even though Rac is important for neutrophil functions. Here, we characterized P-Rex1, a Gbetagamma and PIP(3)-regulated guanine nucleotide exchange factor that was initially identified as a Rac activator in response to Chemoattractants, for its roles in the regulation of Rac activity and neutrophil functions. We generated a mouse line in which the P-Rex1 gene is disrupted and found that P-Rex1 deficiency did not significantly affect Rac1 activation but diminished Rac2 activation in response to a chemoattractant fMLP in mouse neutrophils. This preference for Rac2 may partially result from the apparent higher affinity of P-Rex1 for Rac2 than for Rac1 because P-Rex1 was more readily immunoprecipitated with Rac2(S17N) than Rac1(S17N). In addition, P-Rex1 deficiency significantly attenuated fMLP-induced F actin formation and superoxide production without affecting LPS- or PMA-induced production. Furthermore, P-Rex1 deficiency caused a chemotactic defect that is primarily attributed to a reduction in the migration rate rather than directionality.
Sachie Ishibashi - One of the best experts on this subject based on the ideXlab platform.
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the s100a8 serum amyloid a3 tlr4 paracrine cascade establishes a pre metastatic phase
Nature Cell Biology, 2008Co-Authors: Sachie Hiratsuka, Hiroyuki Aburatani, Akira Watanabe, Yoshiko Sakurai, Sachiko Akashitakamura, Sachie Ishibashi, Kensuke Miyake, Masabumi Shibuya, Shizuo Akira, Yoshiro MaruAbstract:The production of Chemoattractants in the pre-metastatic lung can be induced by distant primary tumours. The Chemoattractants S100A8 and S100A9 induce serum amyloid A3 and TLR4 activation and cause an inflammation-like state that facilitates metastasis. A large number of macrophages and haematopoietic progenitor cells accumulate in pre-metastatic lungs1,2 in which Chemoattractants, such as S100A8 and S100A9, are produced by distant primary tumours serving as metastatic soil3. The exact mechanism by which these Chemoattractants elicit cell accumulation is not known. Here, we show that serum amyloid A (SAA) 3, which is induced in pre-metastatic lungs by S100A8 and S100A9, has a role in the accumulation of myeloid cells and acts as a positive-feedback regulator for chemoattractant secretion. We also show that in lung endothelial cells and macrophages, Toll-like receptor (TLR) 4 acts as a functional receptor for SAA3 in the pre-metastatic phase. In our study, SAA3 stimulated NF-κB signalling in a TLR4-dependent manner and facilitated metastasis. This inflammation-like state accelerated the migration of primary tumour cells to lung tissues, but this was suppressed by the inhibition of either TLR4 or SAA3. Thus, blocking SAA3–TLR4 function in the pre-metastatic phase could prove to be an effective strategy for the prevention of pulmonary metastasis.
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the s100a8 serum amyloid a3 tlr4 paracrine cascade establishes a pre metastatic phase
Nature Cell Biology, 2008Co-Authors: Sachie Hiratsuka, Hiroyuki Aburatani, Akira Watanabe, Yoshiko Sakurai, Sachiko Akashitakamura, Sachie Ishibashi, Kensuke Miyake, Masabumi Shibuya, Shizuo Akira, Yoshiro MaruAbstract:A large number of macrophages and haematopoietic progenitor cells accumulate in pre-metastatic lungs in which Chemoattractants, such as S100A8 and S100A9, are produced by distant primary tumours serving as metastatic soil. The exact mechanism by which these Chemoattractants elicit cell accumulation is not known. Here, we show that serum amyloid A (SAA) 3, which is induced in pre-metastatic lungs by S100A8 and S100A9, has a role in the accumulation of myeloid cells and acts as a positive-feedback regulator for chemoattractant secretion. We also show that in lung endothelial cells and macrophages, Toll-like receptor (TLR) 4 acts as a functional receptor for SAA3 in the pre-metastatic phase. In our study, SAA3 stimulated NF-kappaB signalling in a TLR4-dependent manner and facilitated metastasis. This inflammation-like state accelerated the migration of primary tumour cells to lung tissues, but this was suppressed by the inhibition of either TLR4 or SAA3. Thus, blocking SAA3-TLR4 function in the pre-metastatic phase could prove to be an effective strategy for the prevention of pulmonary metastasis.