The Experts below are selected from a list of 510 Experts worldwide ranked by ideXlab platform
Yehuda Shoenfeld - One of the best experts on this subject based on the ideXlab platform.
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The effect of TPC on arthritis scores in DBA/1J CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:The data are presented as arthritis score of s.c. treated CIA mice, measured from day (0) (disease induction) until day 35 mean ± SD. Tuftsin-phosphorylcholine (TPC) (n = 10), PBS (n = 10), Tuftsin (T) (n = 10), phosphorylcholine (PC) (n = 10), untreated (n = 10). Values are mean ± SD. ***P < 0.001.
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B10 regulatory cells increase in isolated splenocytes of TPC-treated CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:[A] The data are presented as percentage of Breg cells–IL-10+CD5+CD1d+ increase in isolated splenocytes derived from Tuftsin- phosphorylcholine (TPC), PBS, Tuftsin (T), phosphorylcholine (PC), and untreated CIA mice (n = 10). Values are mean ± SD, P < 0.001. [B] Representative flow cytometry analyses of Breg cells–IL-10+CD5+CD1d+ (gated on IL-10+) in isolated splenocytes derived from CIA mice treated with TPC, PBS, T, and PC, as well as untreated CIA mice.
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Cytokine expression by splenocytes from CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:In vitro analyses of concentrations of the pro-inflammatory cytokines IL-1β, IL-17, IL-6, TNF-α, and the anti-inflammatory cytokine IL-10, in the culture fluids of splenocytes originating from Tuftsin-phosphoryl choline (TPC), PBS, Tuftsin (T), phosphorylcholine (PC) and untreated CIA mice. The data are presented as concentration in pg/ml. n = 10 per group. [A] In vitro analyses of the pro-inflammatory cytokine IL-1-β concentration. [B] In vitro analyses of the pro-inflammatory cytokine IL-17 concentration. [C] In vitro analyses of the pro-inflammatory cytokine IL-6 concentration. [D] In vitro analyses of the pro-inflammatory cytokine TNF-α concentration. [E] In vitro analyses of the anti-inflammatory cytokine IL-10 concentration.
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Increase in Treg cells in isolated splenocytes of TPC-treated CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:[A] The data are presented as percentage of Treg cells -CD4+CD25+FOXP3+ expansion in isolated splenocytes of Tuftsin- phosphorylcholine (TPC), PBS, Tuftsin (T), phosphoryl choline (PC), and untreated CIA mice (n = 10). Values are the mean ± SD, P < 0.001. [B] Representative flow cytometry analyses of Treg cells -CD4+CD25+FOXP3+ (gated on CD4+) in isolated splenocytes derived from CIA mice treated with TPC, PBS, T and PC and untreated CIA mice. [C] The data are presented as percentage of Tregs -CD4+CD25+FOXP3+ neuropilin-1+ (NPN1+) expansion in isolated splenocytes of TPC and PBS treated mice (n = 10). Values are the mean ± SD, P < 0.001. [D] Representative flow cytometry analyses of Tregs -CD4+CD25+FOXP3+ neuropilin-1+ NPN1+ (gated on CD4+FOXP3+) in splenocytes derived from the TPC and PBS treated mice P < 0.001.
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Helminths-based bi-functional molecule, Tuftsin-phosphorylcholine (TPC), ameliorates an established murine arthritis.
'Public Library of Science (PLoS)', 2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:A novel small molecule named Tuftsin-phosphorylcholine (TPC), which is linked to the biological activity of helminths, was constructed. The current study address the effect of TPC treatment in established collagen-induced arthritis (CIA) mice and propose TPC bi-functional activity. TPC treatment was initiated when clinical score was 2 to 4. Arthritis scores in TPC treated mice were lower compared to mice treated with vehicle (P < 0.001). Joint staining showed normal joint structure in TPC-treated mice compared to control groups treated with phosphate buffered saline (PBS), phosphorylcholine, or Tuftsin, which exhibited severely inflamed joints. TPC enhanced anti-inflammatory response due to increased IL-10 secretion, and reduced pro-inflammatory cytokine secretion (IL-1-β, IL-6, TNF-αP < 0.001). Furthermore, TPC therapy increased expansion of CD4+CD25+FOXP3+T regulatory cells and IL-10+CD5+CD1d+B regulatory cells. We propose that the immunomodulatory activity of TPC can be a result of a bi-specific activity of TPC: (a) The Tuftsin part of the TPC shifts RAW macrophage cells from pro-inflammatory macrophages M1 to anti-inflammatory M2-secreting IL-10 (P < 0.001) through neuropilin-1 and (b) TPC significantly reduce mouse TLR4 expression via NFkB pathway by HEKTM cells (P < 0.02) via the phosphorylcholine site of the molecule. Our results indicate that TPC, significantly ameliorated established CIA by its immunomodulatory activity. These data could lead to a novel self bi-functional small molecule for treating patients with progressive RA
Stella E. Tsirka - One of the best experts on this subject based on the ideXlab platform.
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Tuftsin Combines With Remyelinating Therapy and Improves Outcomes in Models of CNS Demyelinating Disease
'Frontiers Media SA', 2018Co-Authors: Kaitlyn K. Thompson, Jillian C. Nissen, Amanda Pretory, Stella E. TsirkaAbstract:Though promoting remyelination in multiple sclerosis (MS) has emerged as a promising therapeutic strategy, it does not address inflammatory signals that continue to induce neuronal damage and inhibit effectiveness of repair mechanisms. Our lab has previously characterized the immunomodulatory tetrapeptide, Tuftsin, which induces an anti-inflammatory shift in microglia and macrophages. This targeted anti-inflammatory agent improves physical deficits in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Here, we sought to determine whether Tuftsin is also effective in combination with benztropine, an FDA-approved drug that stimulates remyelination, in both EAE and in the cuprizone model of demyelination. We show that combining these two agents to promote anti-inflammatory and remyelinating mechanisms alleviates symptoms in EAE and lessens pathological hallmarks in both MS models. Importantly, Tuftsin is required to transform the inflammatory CNS environment normally present in EAE/MS into one of an anti-inflammatory nature, and benztropine is required in the cuprizone model to improve remyelination. Our data further support Tuftsin's beneficial immunomodulatory activity in the context of EAE, and show that when studying remyelination in the absence of an autoimmune insult, Tuftsin still activated microglia toward an anti-inflammatory fate, but benztropine was necessary for significant repair of the damaged myelin. Overall, Tuftsin effectively combined with benztropine to significantly improve MS-like pathologies in both models
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Data_Sheet_1_Tuftsin Combines With Remyelinating Therapy and Improves Outcomes in Models of CNS Demyelinating Disease.PDF
2018Co-Authors: Kaitlyn K. Thompson, Jillian C. Nissen, Amanda Pretory, Stella E. TsirkaAbstract:Though promoting remyelination in multiple sclerosis (MS) has emerged as a promising therapeutic strategy, it does not address inflammatory signals that continue to induce neuronal damage and inhibit effectiveness of repair mechanisms. Our lab has previously characterized the immunomodulatory tetrapeptide, Tuftsin, which induces an anti-inflammatory shift in microglia and macrophages. This targeted anti-inflammatory agent improves physical deficits in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Here, we sought to determine whether Tuftsin is also effective in combination with benztropine, an FDA-approved drug that stimulates remyelination, in both EAE and in the cuprizone model of demyelination. We show that combining these two agents to promote anti-inflammatory and remyelinating mechanisms alleviates symptoms in EAE and lessens pathological hallmarks in both MS models. Importantly, Tuftsin is required to transform the inflammatory CNS environment normally present in EAE/MS into one of an anti-inflammatory nature, and benztropine is required in the cuprizone model to improve remyelination. Our data further support Tuftsin's beneficial immunomodulatory activity in the context of EAE, and show that when studying remyelination in the absence of an autoimmune insult, Tuftsin still activated microglia toward an anti-inflammatory fate, but benztropine was necessary for significant repair of the damaged myelin. Overall, Tuftsin effectively combined with benztropine to significantly improve MS-like pathologies in both models.
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Adoptive transfer of Tuftsin and NCM modulated T cells on day 14 ameliorates established EAE.
2012Co-Authors: Jillian C. Nissen, Emily I. Chen, Stella E. TsirkaAbstract:Wild-type (WT) mice were injected with MOG35–55 peptide in CFA and pertussis toxin to induce EAE. Osmotic pumps filled with PBS or 500 µM Tuftsin in PBS were implanted in the back of the mice on day 1 after MOG immunization. 5×106 T cells, modulated as follows: Tuftsin/NCM-treated T cells; Tuftsin-only treated T cells; NCM-only treated T cells, were injected intravenously into recipient C57BL/6 mice immunized with MOG 14 days after the onset of disease (arrow indicates timepoint when T cell transfer was performed) and the disease severity scored as described in Methods. (The experiment was repeated twice. Cumulative data are provided; total number of animals tested, n = 12/PBS-infused mice; n = 12/Tuftsin-infused mice; n = 12/mice adoptively transferred with Tuftsin plus NCM-modulated T cells; n = 5/mice adoptively transferred with Tuftsin-only treated T cells; n = 5/mice adoptively transferred with NCM-only treated T cells). Statistical analysis was performed, as described in the Methods. All time points between Tuftsin/NCM-treated T cells and PBS control were found to be significant (p
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Tuftsin promotes an anti-inflammatory switch and attenuates symptoms in experimental autoimmune encephalomyelitis
2012Co-Authors: Jillian C. Nissen, Emily I. Chen, Stella E. TsirkaAbstract:Multiple sclerosis (MS) is a demyelinating autoimmune disease mediated by infiltration of T cells into the central nervous system after compromise of the blood-brain barrier. We have previously shown that administration of Tuftsin, a macrophage/microglial activator, dramatically improves the clinical course of experimental autoimmune encephalomyelitis (EAE), a well-established animal model for MS. Tuftsin administration correlates with upregulation of the immunosuppres-sive Helper-2 Tcell (Th2) cytokine transcription factor GATA-3. We now show that Tuftsin-mediated microglial activation results in shifting microglia to an anti-inflammatory phenotype. Moreover, the T cell phenotype is shifted towards immunoprotection after exposure to Tuftsin-treated activated microglia; specifically, downregulation of pro-inflammatory Th1 responses is triggered in conjunction with upregulation of Th2-specific responses and expansion of immunosuppressive regulatory T cells (Tregs). Finally, Tuftsin-shifted T cells, delivered into animals via adoptive transfer, reverse the pathology observed in mice with established EAE. Taken together, our findings demonstrate that Tuftsin decreases th
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Treatment of microglia with Tuftsin and excitotoxic media causes an M2 shift.
2012Co-Authors: Jillian C. Nissen, Emily I. Chen, Stella E. TsirkaAbstract:Quantitative RT-PCR was performed to analyze changes in gene expression of the M1 marker TNFα (A) and the M2 marker IL10 (B) in response to Tuftsin and NCM treatment for 10 hours. Primary microglia were treated with increasing concentrations of Tuftsin or Tuftsin and NCM prepared from primary cortical neurons exposed to 100 µM glutamate overnight. (C) The ratio of the fold change of IL10 (M2) to the fold change of TNFα (M1). n = 3, *, p
Tomer Bashi - One of the best experts on this subject based on the ideXlab platform.
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Helminth-Based Product and the Microbiome of Mice with Lupus
American Society for Microbiology, 2019Co-Authors: Hadar Neuman, Mati Fridkin, Tomer Bashi, Iris Barshack, Hadar Mor, Or Givol, Abdulla Watad, Asaf Shemer, Alexander Volkov, Miri BlankAbstract:Recently, several papers referred to the association of different bacteria with lupus in mice and humans. This is the first report to demonstrate the effect of a compound derived from helminths on the induction of remission in mice with lupus and its association with a bacterial change. We show that several genera, including Akkermansia, are associated with clinical and serological parameters of lupus, while other genera, including butyrate-producing bacteria, are associated with amelioration of disease following Tuftsin and phosphorylcholine treatment.The hygiene hypothesis claims that the lack of exposure to microorganisms in developed countries correlates with a rise in the incidence of autoimmune diseases. It was also found that helminths are able to modulate the immune response in hosts in order to survive. Consequently, several successful trials using helminths as a treatment for autoimmune patients have been reported. The helminth derivative, phosphorylcholine (PC), was discovered as an immunomodulatory molecule. We have recently shown in a murine model that when a conjugate of Tuftsin and PC, termed TPC, is prophylactically administered before the onset of glomerulonephritis, it attenuates the development of systemic lupus erythematosus (SLE). The current study aimed to examine the TPC effect on the gut microbiome in a mouse model of lupus. TPC treatment altered the gut composition in the mice with active lupus, in correlation with a significant decrease in glomerulonephritis, followed by an increased level of anti-inflammatory interleukin 10 (IL-10), decreased levels of proinflammatory mediators, and expansion of the T regulatory cell population. Importantly, we found that TPC treatment altered the mouse gut microbiome composition, in correlation with a significant decrease in protein secretion and improved disease parameters. The major effects of TPC treatment on the gut microbiome included decreased abundances of Akkermansia and increased abundance of several genera, including Turicibacter, Bifidobacterium, unclassified Mogibacteriaceae, unclassified Clostridiaceae, Adlercreutzia, Allobaculum, and Anaeroplasma. Overall, our results associate microbial changes with the immunomodulation of glomerulonephritis in mice with lupus
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The effect of TPC on arthritis scores in DBA/1J CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:The data are presented as arthritis score of s.c. treated CIA mice, measured from day (0) (disease induction) until day 35 mean ± SD. Tuftsin-phosphorylcholine (TPC) (n = 10), PBS (n = 10), Tuftsin (T) (n = 10), phosphorylcholine (PC) (n = 10), untreated (n = 10). Values are mean ± SD. ***P < 0.001.
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B10 regulatory cells increase in isolated splenocytes of TPC-treated CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:[A] The data are presented as percentage of Breg cells–IL-10+CD5+CD1d+ increase in isolated splenocytes derived from Tuftsin- phosphorylcholine (TPC), PBS, Tuftsin (T), phosphorylcholine (PC), and untreated CIA mice (n = 10). Values are mean ± SD, P < 0.001. [B] Representative flow cytometry analyses of Breg cells–IL-10+CD5+CD1d+ (gated on IL-10+) in isolated splenocytes derived from CIA mice treated with TPC, PBS, T, and PC, as well as untreated CIA mice.
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Cytokine expression by splenocytes from CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:In vitro analyses of concentrations of the pro-inflammatory cytokines IL-1β, IL-17, IL-6, TNF-α, and the anti-inflammatory cytokine IL-10, in the culture fluids of splenocytes originating from Tuftsin-phosphoryl choline (TPC), PBS, Tuftsin (T), phosphorylcholine (PC) and untreated CIA mice. The data are presented as concentration in pg/ml. n = 10 per group. [A] In vitro analyses of the pro-inflammatory cytokine IL-1-β concentration. [B] In vitro analyses of the pro-inflammatory cytokine IL-17 concentration. [C] In vitro analyses of the pro-inflammatory cytokine IL-6 concentration. [D] In vitro analyses of the pro-inflammatory cytokine TNF-α concentration. [E] In vitro analyses of the anti-inflammatory cytokine IL-10 concentration.
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Increase in Treg cells in isolated splenocytes of TPC-treated CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:[A] The data are presented as percentage of Treg cells -CD4+CD25+FOXP3+ expansion in isolated splenocytes of Tuftsin- phosphorylcholine (TPC), PBS, Tuftsin (T), phosphoryl choline (PC), and untreated CIA mice (n = 10). Values are the mean ± SD, P < 0.001. [B] Representative flow cytometry analyses of Treg cells -CD4+CD25+FOXP3+ (gated on CD4+) in isolated splenocytes derived from CIA mice treated with TPC, PBS, T and PC and untreated CIA mice. [C] The data are presented as percentage of Tregs -CD4+CD25+FOXP3+ neuropilin-1+ (NPN1+) expansion in isolated splenocytes of TPC and PBS treated mice (n = 10). Values are the mean ± SD, P < 0.001. [D] Representative flow cytometry analyses of Tregs -CD4+CD25+FOXP3+ neuropilin-1+ NPN1+ (gated on CD4+FOXP3+) in splenocytes derived from the TPC and PBS treated mice P < 0.001.
Mati Fridkin - One of the best experts on this subject based on the ideXlab platform.
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Helminth-Based Product and the Microbiome of Mice with Lupus
American Society for Microbiology, 2019Co-Authors: Hadar Neuman, Mati Fridkin, Tomer Bashi, Iris Barshack, Hadar Mor, Or Givol, Abdulla Watad, Asaf Shemer, Alexander Volkov, Miri BlankAbstract:Recently, several papers referred to the association of different bacteria with lupus in mice and humans. This is the first report to demonstrate the effect of a compound derived from helminths on the induction of remission in mice with lupus and its association with a bacterial change. We show that several genera, including Akkermansia, are associated with clinical and serological parameters of lupus, while other genera, including butyrate-producing bacteria, are associated with amelioration of disease following Tuftsin and phosphorylcholine treatment.The hygiene hypothesis claims that the lack of exposure to microorganisms in developed countries correlates with a rise in the incidence of autoimmune diseases. It was also found that helminths are able to modulate the immune response in hosts in order to survive. Consequently, several successful trials using helminths as a treatment for autoimmune patients have been reported. The helminth derivative, phosphorylcholine (PC), was discovered as an immunomodulatory molecule. We have recently shown in a murine model that when a conjugate of Tuftsin and PC, termed TPC, is prophylactically administered before the onset of glomerulonephritis, it attenuates the development of systemic lupus erythematosus (SLE). The current study aimed to examine the TPC effect on the gut microbiome in a mouse model of lupus. TPC treatment altered the gut composition in the mice with active lupus, in correlation with a significant decrease in glomerulonephritis, followed by an increased level of anti-inflammatory interleukin 10 (IL-10), decreased levels of proinflammatory mediators, and expansion of the T regulatory cell population. Importantly, we found that TPC treatment altered the mouse gut microbiome composition, in correlation with a significant decrease in protein secretion and improved disease parameters. The major effects of TPC treatment on the gut microbiome included decreased abundances of Akkermansia and increased abundance of several genera, including Turicibacter, Bifidobacterium, unclassified Mogibacteriaceae, unclassified Clostridiaceae, Adlercreutzia, Allobaculum, and Anaeroplasma. Overall, our results associate microbial changes with the immunomodulation of glomerulonephritis in mice with lupus
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The effect of TPC on arthritis scores in DBA/1J CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:The data are presented as arthritis score of s.c. treated CIA mice, measured from day (0) (disease induction) until day 35 mean ± SD. Tuftsin-phosphorylcholine (TPC) (n = 10), PBS (n = 10), Tuftsin (T) (n = 10), phosphorylcholine (PC) (n = 10), untreated (n = 10). Values are mean ± SD. ***P < 0.001.
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B10 regulatory cells increase in isolated splenocytes of TPC-treated CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:[A] The data are presented as percentage of Breg cells–IL-10+CD5+CD1d+ increase in isolated splenocytes derived from Tuftsin- phosphorylcholine (TPC), PBS, Tuftsin (T), phosphorylcholine (PC), and untreated CIA mice (n = 10). Values are mean ± SD, P < 0.001. [B] Representative flow cytometry analyses of Breg cells–IL-10+CD5+CD1d+ (gated on IL-10+) in isolated splenocytes derived from CIA mice treated with TPC, PBS, T, and PC, as well as untreated CIA mice.
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Cytokine expression by splenocytes from CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:In vitro analyses of concentrations of the pro-inflammatory cytokines IL-1β, IL-17, IL-6, TNF-α, and the anti-inflammatory cytokine IL-10, in the culture fluids of splenocytes originating from Tuftsin-phosphoryl choline (TPC), PBS, Tuftsin (T), phosphorylcholine (PC) and untreated CIA mice. The data are presented as concentration in pg/ml. n = 10 per group. [A] In vitro analyses of the pro-inflammatory cytokine IL-1-β concentration. [B] In vitro analyses of the pro-inflammatory cytokine IL-17 concentration. [C] In vitro analyses of the pro-inflammatory cytokine IL-6 concentration. [D] In vitro analyses of the pro-inflammatory cytokine TNF-α concentration. [E] In vitro analyses of the anti-inflammatory cytokine IL-10 concentration.
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Increase in Treg cells in isolated splenocytes of TPC-treated CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:[A] The data are presented as percentage of Treg cells -CD4+CD25+FOXP3+ expansion in isolated splenocytes of Tuftsin- phosphorylcholine (TPC), PBS, Tuftsin (T), phosphoryl choline (PC), and untreated CIA mice (n = 10). Values are the mean ± SD, P < 0.001. [B] Representative flow cytometry analyses of Treg cells -CD4+CD25+FOXP3+ (gated on CD4+) in isolated splenocytes derived from CIA mice treated with TPC, PBS, T and PC and untreated CIA mice. [C] The data are presented as percentage of Tregs -CD4+CD25+FOXP3+ neuropilin-1+ (NPN1+) expansion in isolated splenocytes of TPC and PBS treated mice (n = 10). Values are the mean ± SD, P < 0.001. [D] Representative flow cytometry analyses of Tregs -CD4+CD25+FOXP3+ neuropilin-1+ NPN1+ (gated on CD4+FOXP3+) in splenocytes derived from the TPC and PBS treated mice P < 0.001.
Miri Blank - One of the best experts on this subject based on the ideXlab platform.
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Helminth-Based Product and the Microbiome of Mice with Lupus
American Society for Microbiology, 2019Co-Authors: Hadar Neuman, Mati Fridkin, Tomer Bashi, Iris Barshack, Hadar Mor, Or Givol, Abdulla Watad, Asaf Shemer, Alexander Volkov, Miri BlankAbstract:Recently, several papers referred to the association of different bacteria with lupus in mice and humans. This is the first report to demonstrate the effect of a compound derived from helminths on the induction of remission in mice with lupus and its association with a bacterial change. We show that several genera, including Akkermansia, are associated with clinical and serological parameters of lupus, while other genera, including butyrate-producing bacteria, are associated with amelioration of disease following Tuftsin and phosphorylcholine treatment.The hygiene hypothesis claims that the lack of exposure to microorganisms in developed countries correlates with a rise in the incidence of autoimmune diseases. It was also found that helminths are able to modulate the immune response in hosts in order to survive. Consequently, several successful trials using helminths as a treatment for autoimmune patients have been reported. The helminth derivative, phosphorylcholine (PC), was discovered as an immunomodulatory molecule. We have recently shown in a murine model that when a conjugate of Tuftsin and PC, termed TPC, is prophylactically administered before the onset of glomerulonephritis, it attenuates the development of systemic lupus erythematosus (SLE). The current study aimed to examine the TPC effect on the gut microbiome in a mouse model of lupus. TPC treatment altered the gut composition in the mice with active lupus, in correlation with a significant decrease in glomerulonephritis, followed by an increased level of anti-inflammatory interleukin 10 (IL-10), decreased levels of proinflammatory mediators, and expansion of the T regulatory cell population. Importantly, we found that TPC treatment altered the mouse gut microbiome composition, in correlation with a significant decrease in protein secretion and improved disease parameters. The major effects of TPC treatment on the gut microbiome included decreased abundances of Akkermansia and increased abundance of several genera, including Turicibacter, Bifidobacterium, unclassified Mogibacteriaceae, unclassified Clostridiaceae, Adlercreutzia, Allobaculum, and Anaeroplasma. Overall, our results associate microbial changes with the immunomodulation of glomerulonephritis in mice with lupus
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The effect of TPC on arthritis scores in DBA/1J CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:The data are presented as arthritis score of s.c. treated CIA mice, measured from day (0) (disease induction) until day 35 mean ± SD. Tuftsin-phosphorylcholine (TPC) (n = 10), PBS (n = 10), Tuftsin (T) (n = 10), phosphorylcholine (PC) (n = 10), untreated (n = 10). Values are mean ± SD. ***P < 0.001.
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B10 regulatory cells increase in isolated splenocytes of TPC-treated CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:[A] The data are presented as percentage of Breg cells–IL-10+CD5+CD1d+ increase in isolated splenocytes derived from Tuftsin- phosphorylcholine (TPC), PBS, Tuftsin (T), phosphorylcholine (PC), and untreated CIA mice (n = 10). Values are mean ± SD, P < 0.001. [B] Representative flow cytometry analyses of Breg cells–IL-10+CD5+CD1d+ (gated on IL-10+) in isolated splenocytes derived from CIA mice treated with TPC, PBS, T, and PC, as well as untreated CIA mice.
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Cytokine expression by splenocytes from CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:In vitro analyses of concentrations of the pro-inflammatory cytokines IL-1β, IL-17, IL-6, TNF-α, and the anti-inflammatory cytokine IL-10, in the culture fluids of splenocytes originating from Tuftsin-phosphoryl choline (TPC), PBS, Tuftsin (T), phosphorylcholine (PC) and untreated CIA mice. The data are presented as concentration in pg/ml. n = 10 per group. [A] In vitro analyses of the pro-inflammatory cytokine IL-1-β concentration. [B] In vitro analyses of the pro-inflammatory cytokine IL-17 concentration. [C] In vitro analyses of the pro-inflammatory cytokine IL-6 concentration. [D] In vitro analyses of the pro-inflammatory cytokine TNF-α concentration. [E] In vitro analyses of the anti-inflammatory cytokine IL-10 concentration.
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Increase in Treg cells in isolated splenocytes of TPC-treated CIA mice.
2018Co-Authors: Miri Blank, Mati Fridkin, Tomer Bashi, Ora Shovman, Iris Barshack, Alexander Volkov, Jordan Lachnish, Dana Ben-ami-shor, Miriam Eisenstein, Yehuda ShoenfeldAbstract:[A] The data are presented as percentage of Treg cells -CD4+CD25+FOXP3+ expansion in isolated splenocytes of Tuftsin- phosphorylcholine (TPC), PBS, Tuftsin (T), phosphoryl choline (PC), and untreated CIA mice (n = 10). Values are the mean ± SD, P < 0.001. [B] Representative flow cytometry analyses of Treg cells -CD4+CD25+FOXP3+ (gated on CD4+) in isolated splenocytes derived from CIA mice treated with TPC, PBS, T and PC and untreated CIA mice. [C] The data are presented as percentage of Tregs -CD4+CD25+FOXP3+ neuropilin-1+ (NPN1+) expansion in isolated splenocytes of TPC and PBS treated mice (n = 10). Values are the mean ± SD, P < 0.001. [D] Representative flow cytometry analyses of Tregs -CD4+CD25+FOXP3+ neuropilin-1+ NPN1+ (gated on CD4+FOXP3+) in splenocytes derived from the TPC and PBS treated mice P < 0.001.
