The Experts below are selected from a list of 189135 Experts worldwide ranked by ideXlab platform
Yuan Zhang - One of the best experts on this subject based on the ideXlab platform.
-
fenoterol inhibits lps induced ampk activation and Inflammatory Cytokine production through β arrestin 2 in thp 1 cell line
Biochemical and Biophysical Research Communications, 2015Co-Authors: Wei Wang, Yuan ZhangAbstract:The AMP-activated protein kinase (AMPK) pathway is involved in regulating inflammation in several cell lines. We reported that fenoterol, a β2-adrenergic receptor (β2-AR) agonist, had anti-Inflammatory effects in THP-1 cells, a monocytic cell line. Whether the fenoterol anti-Inflammatory effect involves the AMPK pathway is unknown. In this study, we explored the mechanism of β2-AR stimulation with fenoterol in a lipopolysaccharide (LPS)-induced Inflammatory Cytokine secretion in THP-1 cells. We studied whether fenoterol and β-arrestin-2 or AMPKα1 subunit knockdown could affect LPS-induced AMPK activation, nuclear factor-kappa B (NF-κB) activation and Inflammatory Cytokine secretion. LPS-induced AMPK activation and interleukin 1β (IL-1β) release were reduced with fenoterol pretreatment of THP-1 cells. SiRNA knockdown of β-arrestin-2 abolished the fenoterol inhibition of LPS-induced AMPK activation and interleukin 1β (IL-1β) release, thus β-arrestin-2 mediated the anti-Inflammatory effects of fenoterol on LPS-treated THP-1 cells. In addition, siRNA knockdown of AMPKα1 significantly attenuated the LPS-induced NF-κB activation and IL-1β release, so AMPKα1 was a key signaling molecule involved in LPS-induced Inflammatory Cytokine production. These results suggested the β2-AR agonist fenoterol inhibited LPS-induced AMPK activation and IL-1β release via β-arrestin-2 in THP-1 cells. The exploration of these mechanisms may help optimize therapeutic agents targeting these pathways in Inflammatory diseases.
Hagir B. Suliman - One of the best experts on this subject based on the ideXlab platform.
-
heme oxygenase 1 couples activation of mitochondrial biogenesis to anti Inflammatory Cytokine expression
Journal of Biological Chemistry, 2011Co-Authors: Claude A. Piantadosi, Karen E Weltywolf, Crystal M Withers, Raquel R Bartz, Nancy Chou Macgarvey, Ping Fu, Timothy E Sweeney, Hagir B. SulimanAbstract:Abstract The induction of heme oxygenase-1 (HO-1; Hmox1) by inflammation, for instance in sepsis, is associated both with an anti-Inflammatory response and with mitochondrial biogenesis. Here, we tested the idea that HO-1, acting through the Nfe2l2 (Nrf2) transcription factor, links anti-Inflammatory Cytokine expression to activation of mitochondrial biogenesis. HO-1 induction after lipopolysaccharide (LPS) stimulated anti-Inflammatory interleukin (IL)-10 and IL-1 receptor antagonist (IL-1Ra) expression in mouse liver, human HepG2 cells, and mouse J774.1 macrophages, but blunted tumor necrosis factor-alpha expression. This was accompanied by nuclear Nfe2l2 accumulation, and led us to identify abundant Nfe2l2 and other mitochondrial biogenesis transcription factor binding sites in the promoter regions of IL10 and IL1Ra compared with pro-Inflammatory genes regulated by NF-kB. Mechanistically, HO-1, through its CO product, enabled these transcription factors to bind the core IL10 and IL1Ra promoters, which for IL10 included Nfe2l2, nuclear respiratory factor (NRF)-2 (GABPA), and MEF2, and for IL1Ra, NRF-1 and MEF2. In cells, Hmox1 or Nfe2l2 RNA silencing prevented IL-10 and IL-1Ra up-regulation, and HO-1 induction failed post-LPS in Nfe2l2-silenced cells and post-sepsis in Nfe2l2-/- mice. Nfe2l2-/- mice compared with WT mice, showed more liver damage, higher mortality, and ineffective CO rescue in sepsis. Nfe2l2-/- mice in sepsis also generated higher hepatic TNF-alpha mRNA levels, lower NRF-1 and PGC-1alpha mRNA levels, and no enhancement of anti-Inflammatory Il10, Socs3 or BclXL gene expression. These findings disclose a highly-structured transcriptional network that couples mitochondrial biogenesis to counter-inflammation with major implications for immune suppression in sepsis.
-
heme oxygenase 1 couples activation of mitochondrial biogenesis to anti Inflammatory Cytokine expression
Journal of Biological Chemistry, 2011Co-Authors: Claude A. Piantadosi, Karen E Weltywolf, Crystal M Withers, Raquel R Bartz, Nancy Chou Macgarvey, Timothy E Sweeney, Hagir B. SulimanAbstract:The induction of heme oxygenase-1 (HO-1; Hmox1) by inflammation, for instance in sepsis, is associated both with an anti-Inflammatory response and with mitochondrial biogenesis. Here, we tested the idea that HO-1, acting through the Nfe2l2 (Nrf2) transcription factor, links anti-Inflammatory Cytokine expression to activation of mitochondrial biogenesis. HO-1 induction after LPS stimulated anti-Inflammatory IL-10 and IL-1 receptor antagonist (IL-1Ra) expression in mouse liver, human HepG2 cells, and mouse J774.1 macrophages but blunted tumor necrosis factor-α expression. This was accompanied by nuclear Nfe2l2 accumulation and led us to identify abundant Nfe2l2 and other mitochondrial biogenesis transcription factor binding sites in the promoter regions of IL10 and IL1Ra compared with pro-Inflammatory genes regulated by NF-κΒ. Mechanistically, HO-1, through its CO product, enabled these transcription factors to bind the core IL10 and IL1Ra promoters, which for IL10 included Nfe2l2, nuclear respiratory factor (NRF)-2 (Gabpa), and MEF2, and for IL1Ra, included NRF-1 and MEF2. In cells, Hmox1 or Nfe2l2 RNA silencing prevented IL-10 and IL-1Ra up-regulation, and HO-1 induction failed post-LPS in Nfe2l2-silenced cells and post-sepsis in Nfe2l2−/− mice. Nfe2l2−/− mice compared with WT mice, showed more liver damage, higher mortality, and ineffective CO rescue in sepsis. Nfe2l2−/− mice in sepsis also generated higher hepatic TNF-α mRNA levels, lower NRF-1 and PGC-1α mRNA levels, and no enhancement of anti-Inflammatory Il10, Socs3, or bcl-xL gene expression. These findings disclose a highly structured transcriptional network that couples mitochondrial biogenesis to counter-inflammation with major implications for immune suppression in sepsis.
Christian D Muller - One of the best experts on this subject based on the ideXlab platform.
-
celastrol inhibits pro Inflammatory Cytokine secretion in crohn s disease biopsies
Biochemical and Biophysical Research Communications, 2004Co-Authors: Guillaume Pinna, Marc Fiorucci, Jeanmarie Reimund, Nathalie Taquet, Yves Arondel, Christian D MullerAbstract:Crohn's disease is a chronic intestinal Inflammatory process. In modern therapy, TNF-alpha inhibition is the main goal. The aim here is to characterize the effects of Celastrol, a pentacyclic-triterpene, on the secretion of Inflammatory Cytokines by LPS-activated human cells. Celastrol dose-dependently inhibited the secretion of all tested pro-Inflammatory Cytokines with IC(50) in the nanomolar range. Effect not related to glucocorticoid receptor activity is shown by competition experiments with the steroid antagonist RU486. Celastrol inhibited the pro-Inflammatory Cytokine secretion from mucosal Inflammatory biopsies from Crohn's disease patients. Cytometry emphasized that for all tested pro-Inflammatory Cytokines, CD33(+) cells are the most sensitive. Quantitative-PCR and confocal analysis on a human monocytic cell line indicated that Celastrol acts at the transcriptional level by inhibiting LPS-induced NF-kappaB translocation. Celastrol might be a putative anti-Inflammatory drug in the treatment of Inflammatory diseases, given its inhibition of Cytokine production by intestinal biopsies from Crohn's disease patients.
-
mucosal Inflammatory Cytokine production by intestinal biopsies in patients with ulcerative colitis and crohn s disease
Journal of Clinical Immunology, 1996Co-Authors: Jeanmarie Reimund, Christian D Muller, C Wittersheim, S Dumont, R Baumann, P Poindron, B DuclosAbstract:Chronic inflammation in Inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) may be attributed partly to increased secretion of Inflammatory Cytokines. The aim of this study was to investigate simultaneously the spontaneous release patterns of tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), and interleukin-6 (IL-6) by organ cultures of inflamed mucosa from IBD patients. Organ cultures of involved IBD mucosa spontaneously produced increased amounts of TNF-α, IL-1β, and IL-6 compared to normal mucosa. The patterns of Cytokine release between Crohn's disease and ulcerative colitis organ cultures were not significantly different. Increased Inflammatory Cytokine production by lamina propria mononuclear cells (LPMCs) and mucosa treated with EDTA suggests that these Cytokines originate mainly from LPMCs. These results confirm the role of Inflammatory Cytokines in IBD and shed a new light on the role of TNF-α in IBD.
Jeanmarie Reimund - One of the best experts on this subject based on the ideXlab platform.
-
celastrol inhibits pro Inflammatory Cytokine secretion in crohn s disease biopsies
Biochemical and Biophysical Research Communications, 2004Co-Authors: Guillaume Pinna, Marc Fiorucci, Jeanmarie Reimund, Nathalie Taquet, Yves Arondel, Christian D MullerAbstract:Crohn's disease is a chronic intestinal Inflammatory process. In modern therapy, TNF-alpha inhibition is the main goal. The aim here is to characterize the effects of Celastrol, a pentacyclic-triterpene, on the secretion of Inflammatory Cytokines by LPS-activated human cells. Celastrol dose-dependently inhibited the secretion of all tested pro-Inflammatory Cytokines with IC(50) in the nanomolar range. Effect not related to glucocorticoid receptor activity is shown by competition experiments with the steroid antagonist RU486. Celastrol inhibited the pro-Inflammatory Cytokine secretion from mucosal Inflammatory biopsies from Crohn's disease patients. Cytometry emphasized that for all tested pro-Inflammatory Cytokines, CD33(+) cells are the most sensitive. Quantitative-PCR and confocal analysis on a human monocytic cell line indicated that Celastrol acts at the transcriptional level by inhibiting LPS-induced NF-kappaB translocation. Celastrol might be a putative anti-Inflammatory drug in the treatment of Inflammatory diseases, given its inhibition of Cytokine production by intestinal biopsies from Crohn's disease patients.
-
mucosal Inflammatory Cytokine production by intestinal biopsies in patients with ulcerative colitis and crohn s disease
Journal of Clinical Immunology, 1996Co-Authors: Jeanmarie Reimund, Christian D Muller, C Wittersheim, S Dumont, R Baumann, P Poindron, B DuclosAbstract:Chronic inflammation in Inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) may be attributed partly to increased secretion of Inflammatory Cytokines. The aim of this study was to investigate simultaneously the spontaneous release patterns of tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), and interleukin-6 (IL-6) by organ cultures of inflamed mucosa from IBD patients. Organ cultures of involved IBD mucosa spontaneously produced increased amounts of TNF-α, IL-1β, and IL-6 compared to normal mucosa. The patterns of Cytokine release between Crohn's disease and ulcerative colitis organ cultures were not significantly different. Increased Inflammatory Cytokine production by lamina propria mononuclear cells (LPMCs) and mucosa treated with EDTA suggests that these Cytokines originate mainly from LPMCs. These results confirm the role of Inflammatory Cytokines in IBD and shed a new light on the role of TNF-α in IBD.
Claude A. Piantadosi - One of the best experts on this subject based on the ideXlab platform.
-
heme oxygenase 1 couples activation of mitochondrial biogenesis to anti Inflammatory Cytokine expression
Journal of Biological Chemistry, 2011Co-Authors: Claude A. Piantadosi, Karen E Weltywolf, Crystal M Withers, Raquel R Bartz, Nancy Chou Macgarvey, Ping Fu, Timothy E Sweeney, Hagir B. SulimanAbstract:Abstract The induction of heme oxygenase-1 (HO-1; Hmox1) by inflammation, for instance in sepsis, is associated both with an anti-Inflammatory response and with mitochondrial biogenesis. Here, we tested the idea that HO-1, acting through the Nfe2l2 (Nrf2) transcription factor, links anti-Inflammatory Cytokine expression to activation of mitochondrial biogenesis. HO-1 induction after lipopolysaccharide (LPS) stimulated anti-Inflammatory interleukin (IL)-10 and IL-1 receptor antagonist (IL-1Ra) expression in mouse liver, human HepG2 cells, and mouse J774.1 macrophages, but blunted tumor necrosis factor-alpha expression. This was accompanied by nuclear Nfe2l2 accumulation, and led us to identify abundant Nfe2l2 and other mitochondrial biogenesis transcription factor binding sites in the promoter regions of IL10 and IL1Ra compared with pro-Inflammatory genes regulated by NF-kB. Mechanistically, HO-1, through its CO product, enabled these transcription factors to bind the core IL10 and IL1Ra promoters, which for IL10 included Nfe2l2, nuclear respiratory factor (NRF)-2 (GABPA), and MEF2, and for IL1Ra, NRF-1 and MEF2. In cells, Hmox1 or Nfe2l2 RNA silencing prevented IL-10 and IL-1Ra up-regulation, and HO-1 induction failed post-LPS in Nfe2l2-silenced cells and post-sepsis in Nfe2l2-/- mice. Nfe2l2-/- mice compared with WT mice, showed more liver damage, higher mortality, and ineffective CO rescue in sepsis. Nfe2l2-/- mice in sepsis also generated higher hepatic TNF-alpha mRNA levels, lower NRF-1 and PGC-1alpha mRNA levels, and no enhancement of anti-Inflammatory Il10, Socs3 or BclXL gene expression. These findings disclose a highly-structured transcriptional network that couples mitochondrial biogenesis to counter-inflammation with major implications for immune suppression in sepsis.
-
heme oxygenase 1 couples activation of mitochondrial biogenesis to anti Inflammatory Cytokine expression
Journal of Biological Chemistry, 2011Co-Authors: Claude A. Piantadosi, Karen E Weltywolf, Crystal M Withers, Raquel R Bartz, Nancy Chou Macgarvey, Timothy E Sweeney, Hagir B. SulimanAbstract:The induction of heme oxygenase-1 (HO-1; Hmox1) by inflammation, for instance in sepsis, is associated both with an anti-Inflammatory response and with mitochondrial biogenesis. Here, we tested the idea that HO-1, acting through the Nfe2l2 (Nrf2) transcription factor, links anti-Inflammatory Cytokine expression to activation of mitochondrial biogenesis. HO-1 induction after LPS stimulated anti-Inflammatory IL-10 and IL-1 receptor antagonist (IL-1Ra) expression in mouse liver, human HepG2 cells, and mouse J774.1 macrophages but blunted tumor necrosis factor-α expression. This was accompanied by nuclear Nfe2l2 accumulation and led us to identify abundant Nfe2l2 and other mitochondrial biogenesis transcription factor binding sites in the promoter regions of IL10 and IL1Ra compared with pro-Inflammatory genes regulated by NF-κΒ. Mechanistically, HO-1, through its CO product, enabled these transcription factors to bind the core IL10 and IL1Ra promoters, which for IL10 included Nfe2l2, nuclear respiratory factor (NRF)-2 (Gabpa), and MEF2, and for IL1Ra, included NRF-1 and MEF2. In cells, Hmox1 or Nfe2l2 RNA silencing prevented IL-10 and IL-1Ra up-regulation, and HO-1 induction failed post-LPS in Nfe2l2-silenced cells and post-sepsis in Nfe2l2−/− mice. Nfe2l2−/− mice compared with WT mice, showed more liver damage, higher mortality, and ineffective CO rescue in sepsis. Nfe2l2−/− mice in sepsis also generated higher hepatic TNF-α mRNA levels, lower NRF-1 and PGC-1α mRNA levels, and no enhancement of anti-Inflammatory Il10, Socs3, or bcl-xL gene expression. These findings disclose a highly structured transcriptional network that couples mitochondrial biogenesis to counter-inflammation with major implications for immune suppression in sepsis.
