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10.1186/s12967-020-02626-z http://scihub22266oqcxt.onion/10.1186/s12967-020-02626-z 33256749!7702209!33256749     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Transl+Med 2020 ; 18 (1): 452 Nephropedia Template TP {{tp|p=33256749|t=2020. LMWF5A suppresses cytokine release by modulating select inflammatory transcription factor activity in stimulated PBMC |pdf=|usr=}}{{33256749}} gab.com Text LMWF5A suppresses cytokine release by modulating select inflammatory transcription factor activity in stimulated PBMC JO: J Transl Med http://www.kidney.de/pget.php?&tw=1&pmid=33256749 #FOAvip BACKGROUND: Dysregulation of transcription and cytokine expression has been implicated in the pathogenesis of a variety inflammatory diseases. The resulting imbalance between inflammatory and resolving transcriptional programs can cause an overabundance of pro-inflammatory, classically activated macrophage type 1 (M1) and/or helper T cell type 1 (Th1) products, such as IFNgamma, TNFalpha, IL1-beta, and IL12, that prevent immune switching to resolution and healing. The low molecular weight fraction of human serum albumin (LMWF5A) is a novel biologic drug that is currently under clinical investigation for the treatment of osteoarthritis and the hyper-inflammatory response associated with COVID-19. This study aims to elucidate transcriptional mechanisms of action involved with the ability of LMWF5A to reduce pro-inflammatory cytokine release. METHODS: ELISA arrays were used to identify cytokines and chemokines influenced by LMWF5A treatment of LPS-stimulated peripheral blood mononuclear cells (PBMC). The resulting profiles were analyzed by gene enrichment to gain mechanistic insight into the biologic processes and transcription factors (TFs) underlying the identified differentially expressed cytokines. DNA-binding ELISAs, luciferase reporter assays, and TNFalpha or IL-1beta relative potency were then employed to confirm the involvement of enriched pathways and TFs. RESULTS: LMWF5A was found to significantly inhibit a distinct set of pro-inflammatory cytokines (TNFalpha, IL-1beta, IL-12, CXCL9, CXCL10, and CXCL11) associated with pro-inflammatory M1/Th1 immune profiles. Gene enrichment analysis also suggests these cytokines are, in part, regulated by NF-kappaB and STAT transcription factors. Data from DNA-binding and reporter assays support this with LMWF5A inhibition of STAT1alpha DNA-binding activity as well as a reduction in overall NF-kappaB-driven luciferase expression. Experiments using antagonists specific for the immunomodulatory and NF-kappaB/STAT-repressing transcription factors, peroxisome proliferator-activated receptor (PPAR)gamma and aryl hydrocarbon receptor (AhR), indicate these pathways are involved in the LMWF5A mechanisms of action by reducing LMWF5A drug potency as measured by TNFalpha and IL-1beta release. CONCLUSION: In this report, we provide evidence that LMWF5A reduces pro-inflammatory cytokine release by activating the immunoregulatory transcription factors PPARgamma and AhR. In addition, our data indicate that LMWF5A suppresses NF-kappaB and STAT1alpha pro-inflammatory pathways. This suggests that LMWF5A acts through these mechanisms to decrease pro-inflammatory transcription factor activity and subsequent inflammatory cytokine production. Twit Text FOAVip LMWF5A suppresses cytokine release by modulating select inflammatory transcription factor activity in stimulated PBMC ????J Transl Med http://www.kidney.de/pget.php?&tw=1&pmid=33256749 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33256749 #FOAvip English Wikipedia <ref>{{Cite pmid|33256749}}</ref> LMWF5A suppresses cytokine release by modulating select inflammatory transcription factor activity in stimulated PBMC #MMPMID33256749 Thomas G; Frederick E; Thompson L; Bar-Or R; Mulugeta Y; Hausburg M; Roshon M; Mains C; Bar-Or D J Transl Med 2020[Nov]; 18 (1): 452 PMID33256749show ga BACKGROUND: Dysregulation of transcription and cytokine expression has been implicated in the pathogenesis of a variety inflammatory diseases. The resulting imbalance between inflammatory and resolving transcriptional programs can cause an overabundance of pro-inflammatory, classically activated macrophage type 1 (M1) and/or helper T cell type 1 (Th1) products, such as IFNgamma, TNFalpha, IL1-beta, and IL12, that prevent immune switching to resolution and healing. The low molecular weight fraction of human serum albumin (LMWF5A) is a novel biologic drug that is currently under clinical investigation for the treatment of osteoarthritis and the hyper-inflammatory response associated with COVID-19. This study aims to elucidate transcriptional mechanisms of action involved with the ability of LMWF5A to reduce pro-inflammatory cytokine release. METHODS: ELISA arrays were used to identify cytokines and chemokines influenced by LMWF5A treatment of LPS-stimulated peripheral blood mononuclear cells (PBMC). The resulting profiles were analyzed by gene enrichment to gain mechanistic insight into the biologic processes and transcription factors (TFs) underlying the identified differentially expressed cytokines. DNA-binding ELISAs, luciferase reporter assays, and TNFalpha or IL-1beta relative potency were then employed to confirm the involvement of enriched pathways and TFs. RESULTS: LMWF5A was found to significantly inhibit a distinct set of pro-inflammatory cytokines (TNFalpha, IL-1beta, IL-12, CXCL9, CXCL10, and CXCL11) associated with pro-inflammatory M1/Th1 immune profiles. Gene enrichment analysis also suggests these cytokines are, in part, regulated by NF-kappaB and STAT transcription factors. Data from DNA-binding and reporter assays support this with LMWF5A inhibition of STAT1alpha DNA-binding activity as well as a reduction in overall NF-kappaB-driven luciferase expression. Experiments using antagonists specific for the immunomodulatory and NF-kappaB/STAT-repressing transcription factors, peroxisome proliferator-activated receptor (PPAR)gamma and aryl hydrocarbon receptor (AhR), indicate these pathways are involved in the LMWF5A mechanisms of action by reducing LMWF5A drug potency as measured by TNFalpha and IL-1beta release. CONCLUSION: In this report, we provide evidence that LMWF5A reduces pro-inflammatory cytokine release by activating the immunoregulatory transcription factors PPARgamma and AhR. In addition, our data indicate that LMWF5A suppresses NF-kappaB and STAT1alpha pro-inflammatory pathways. This suggests that LMWF5A acts through these mechanisms to decrease pro-inflammatory transcription factor activity and subsequent inflammatory cytokine production. |Anti-Inflammatory Agents/pharmacology[MESH] |COVID-19 Drug Treatment[MESH] |COVID-19/immunology/pathology[MESH] |Cells, Cultured[MESH] |Cytokines/*metabolism[MESH] |Gene Expression Regulation/drug effects[MESH] |HEK293 Cells[MESH] |Humans[MESH] |Inflammation Mediators/metabolism[MESH] |Inflammation/genetics/metabolism/*prevention & control[MESH] |Interferon-Stimulated Gene Factor 3/metabolism[MESH] |Leukocytes, Mononuclear/*drug effects/metabolism[MESH] |Lipopolysaccharides[MESH] |Lymphocyte Activation/drug effects[MESH] |Molecular Weight[MESH] |NF-kappa B/metabolism[MESH] |Serum Albumin, Human/chemistry/*pharmacology[MESH] |Signal Transduction/drug effects/genetics/immunology[MESH]LMWF5A suppresses cytokine release by modulating select inflammatory (epmc).pdf DeepDyve Pubget Overpricing