A polymeric nanoparticle formulation of curcumin (NanoCurc™) ameliorates CCl4-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation

Previous data indicated the protective effect of date fruit extract on oxidative damage in rat liver. However, the hepatoprotective effects via other mechanisms have not been investigated. This study was performed to evaluate the antifibrotic effect of date flesh extract (DFE) or date pits extract (DPE) via inactivation of hepatic stellate cells (HSCs), reducing the levels of inflammatory, fibrotic and angiogenic markers. Coffee was used as reference hepatoprotective agent. Liver fibrosis was induced by injection of CCl4(0.4 mL/kg) three times weekly for 8 weeks. DFE, DPE (6 mL/kg), coffee (300 mg/kg), and combination of coffee + DFE and coffee + DPE were given to CCl4-intoxicated rats daily for 8 weeks. DFE, DPE, and their combination with coffee attenuated the elevated levels of inflammatory cytokines including tumor necrosis factor-α, interleukin-6, and interleukin-1β. The increased levels of transforming growth factor-β1 and collagen deposition in injured liver were alleviated by both extracts. CCl4-induced expression ofα-smooth muscle actin was suppressed indicating HSCs inactivation. Increased angiogenesis was ameliorated as revealed by reduced levels and expression of vascular endothelial growth factor and CD31. We concluded that DFE or DPE could protect liver via different mechanisms. The combination of coffee with DFE or DPE may enhance its antifibrotic effects.

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Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines

World Journal of Gastroenterology ◽

10.3748/wjg.v21.i5.1531 ◽

2015 ◽

Vol 21 (5) ◽

pp. 1531 ◽

Cited By ~ 29

Author(s):

Dong-Hong Lu

Keyword(s):

Inflammatory Cytokines ◽

Hepatic Stellate Cell ◽

Cell Activation ◽

Stellate Cell ◽

Interleukin 22 ◽

Hepatic Stellate Cell Activation ◽

Liver Fibrogenesis

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Apoptotic Blebs From Leukemic Cells as a Source of Tumor Associated Antigen for Monocyte-Derived Dendritic Cell Loading

Blood ◽

10.1182/blood.v116.21.3283.3283 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3283-3283

Author(s):

Jurjen M Ruben ◽

Hetty J Bontkes ◽

Theresia M. Westers ◽

Willemijn van Den Ancker ◽

Gert J. Ossenkoppele ◽

...

Keyword(s):

Inflammatory Cytokines ◽

T Cell Activation ◽

Cell Activation ◽

Conflicts Of Interest ◽

Residual Disease ◽

Apoptotic Cell ◽

Leukemic Cells ◽

Cd40 Ligation ◽

Pro Inflammatory Cytokines

Abstract Abstract 3283 Whereas in 80% of the patients suffering from acute myeloid leukemia (AML) complete remission is achieved, the 5-year survival rate is only 30% - 40% due to relapse of the disease. In order to increase overall survival of AML patients, novel or additional therapies are required. Due to their ability to ingest, process and subsequently present antigens to (naïve) lymphocytes in an immunogenic context, dendritic cells (DC) can initiate antigen-specific immunity. Therefore, DC have become a major subject of interest as mediators of anti-tumor immunity in a minimal residual disease setting in AML. Since only few AML-associated antigens (LAA) have been characterized to date, the use of apoptotic tumor blast cells as a source of LAA could be instrumental, due to the presence of both known and unknown LAA. However, the immunogenicity of apoptotic cells remains questionable; e.g. apoptotic tumor cells may not activate DC adequately, but rather impair their function. Previously, it was shown in mice that apoptotic blebs, which detach from the main apoptotic cell during apoptosis, induce DC maturation, whereas the apoptotic cell remnant (ACR) does not. Here, we analyzed monocyte-derived DC (MoDC) function in vitro, after co-culture with either human AML-derived ACR or blebs. Apoptosis of CFSE-labeled HL60 AML cells was induced by Mitoxantrone and ACR and blebs were isolated by differential centrifugation. The apoptotic fractions were subsequently added to allogeneic MoDC without the addition of a maturation stimulus (immature), or with the addition of the cytokine cocktail IL-1β, IL-6, PGE2, and TNFα, supplemented with TLR 7/8 ligand R848, 1 hour after initiation of the co-culture (maturing). Blebs were preferentially ingested compared to ACR by both immature and maturing MoDC (75% vs. 45%, and 75% vs. 40% CFSE positive MoDC (p =< 0.0001), respectively). Analysis of the capacity of mature MoDC to migrate towards the lymph node-homing chemokine CCL19, in a transwell migration system, demonstrated that MoDC migration was diminished by approximately 50% compared to unloaded mature MoDC, irrespective of the ingestion of blebs or ACR. However, the percentage of CFSE-positive MoDC which were able to migrate towards CCL19 was significantly higher when MoDC had ingested blebs, compared to ACR (18% vs. 7% (p = 0.05), respectively). Although the ingestion of blebs or ACR does not lead to significant changes in phenotypic maturation, CD40 ligation of immature MoDC that had taken up blebs, resulted in the secretion of twice the amount of the pro-inflammatory cytokines IL-6 and IL-12p70 as compared to MoDC that had ingested ACR (p = 0.05). In conclusion, we show that blebs derived from human AML cells are preferentially ingested by both immature and maturing MoDC and that a higher percentage of these MoDC are able to migrate towards CCL19, compared to MoDC that have ingested ACR. Furthermore, compared to ACR, ingestion of blebs by MoDC leads to an increased production of the pro-inflammatory cytokines IL-6 and IL-12. Additional functional analyses are underway to determine whether ingestion of blebs also leads to a more efficient antigen presentation and subsequent anti-leukemic T cell activation. Disclosures: No relevant conflicts of interest to declare.

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Association of pro-inflammatory cytokines and T-cell activation marker with CA-125 levels in obese patients with heart failure: Implications for complex immunoinflammatory pathophysiology

Medical Science Monitor ◽

10.12659/msm.881885 ◽

2011 ◽

Vol 17 (8) ◽

pp. LE5-LE6 ◽

Cited By ~ 1

Author(s):

Osman Beton ◽

Mehmet Birhan Yılmaz ◽

Okan Turgut ◽

Izzet Tandogan

Keyword(s):

Heart Failure ◽

T Cell ◽

Inflammatory Cytokines ◽

T Cell Activation ◽

Cell Activation ◽

Ca 125 ◽

Obese Patients ◽

Cell Activation Marker ◽

Patients With Heart Failure ◽

Pro Inflammatory Cytokines

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Alcoholic Hepatitis: A Review

Alcohol and Alcoholism ◽

10.1093/alcalc/agz036 ◽

2019 ◽

Vol 54 (4) ◽

pp. 408-416 ◽

Cited By ~ 5

Author(s):

Nooshin Hosseini ◽

Julia Shor ◽

Gyongyi Szabo

Keyword(s):

Alcohol Use ◽

Alcoholic Hepatitis ◽

Hepatitis A ◽

Cell Activation ◽

Genetic Factors ◽

Inflammatory Cell ◽

Stellate Cell ◽

Hepatic Inflammation ◽

Hepatocyte Damage ◽

Pro Inflammatory Cytokines

Abstract Alcoholic liver disease (ALD) represents a spectrum of injury, ranging from simple steatosis to alcoholic hepatitis to cirrhosis. Regular alcohol use results in fatty changes in the liver which can develop into inflammation, fibrosis and ultimately cirrhosis with continued, excessive drinking. Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality that can occur in patients with steatosis or underlying cirrhosis. The pathogenesis of ALD is multifactorial and in addition to genetic factors, alcohol-induced hepatocyte damage, reactive oxygen species, gut-derived microbial components result in steatosis and inflammatory cell (macrophage and neutrophil leukocyte) recruitment and activation in the liver. Continued alcohol and pro-inflammatory cytokines induce stellate cell activation and result in progressive fibrosis. Other than cessation of alcohol use, medical therapy of AH is limited to prednisolone in a subset of patients. Given the high mortality of AH and the progressive nature of ALD, there is a major need for new therapeutic intervention for this underserved patient population.

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Neuroinflammatory processes are augmented in mice overexpressing human heat-shock protein B1 following ethanol-induced brain injury

Journal of Neuroinflammation ◽

10.1186/s12974-020-02070-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Brigitta Dukay ◽

Fruzsina R. Walter ◽

Judit P. Vigh ◽

Beáta Barabási ◽

Petra Hajdu ◽

...

Keyword(s):

Brain Injury ◽

Heat Shock ◽

Heat Shock Protein ◽

Glial Cell ◽

Inflammatory Cytokines ◽

Cell Activation ◽

Mrna Level ◽

Wild Type ◽

Pro Inflammatory Cytokines

Abstract Background Heat-shock protein B1 (HSPB1) is among the most well-known and versatile member of the evolutionarily conserved family of small heat-shock proteins. It has been implicated to serve a neuroprotective role against various neurological disorders via its modulatory activity on inflammation, yet its exact role in neuroinflammation is poorly understood. In order to shed light on the exact mechanism of inflammation modulation by HSPB1, we investigated the effect of HSPB1 on neuroinflammatory processes in an in vivo and in vitro model of acute brain injury. Methods In this study, we used a transgenic mouse strain overexpressing the human HSPB1 protein. In the in vivo experiments, 7-day-old transgenic and wild-type mice were treated with ethanol. Apoptotic cells were detected using TUNEL assay. The mRNA and protein levels of cytokines and glial cell markers were examined using RT-PCR and immunohistochemistry in the brain. We also established primary neuronal, astrocyte, and microglial cultures which were subjected to cytokine and ethanol treatments. TNFα and hHSPB1 levels were measured from the supernates by ELISA, and intracellular hHSPB1 expression was analyzed using fluorescent immunohistochemistry. Results Following ethanol treatment, the brains of hHSPB1-overexpressing mice showed a significantly higher mRNA level of pro-inflammatory cytokines (Tnf, Il1b), microglia (Cd68, Arg1), and astrocyte (Gfap) markers compared to wild-type brains. Microglial activation, and 1 week later, reactive astrogliosis was higher in certain brain areas of ethanol-treated transgenic mice compared to those of wild-types. Despite the remarkably high expression of pro-apoptotic Tnf, hHSPB1-overexpressing mice did not exhibit higher level of apoptosis. Our data suggest that intracellular hHSPB1, showing the highest level in primary astrocytes, was responsible for the inflammation-regulating effects. Microglia cells were the main source of TNFα in our model. Microglia isolated from hHSPB1-overexpressing mice showed a significantly higher release of TNFα compared to wild-type cells under inflammatory conditions. Conclusions Our work provides novel in vivo evidence that hHSPB1 overexpression has a regulating effect on acute neuroinflammation by intensifying the expression of pro-inflammatory cytokines and enhancing glial cell activation, but not increasing neuronal apoptosis. These results suggest that hHSPB1 may play a complex role in the modulation of the ethanol-induced neuroinflammatory response.

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The IL-33/ST2 axis augments effector T-cell responses during acute GVHD

Blood ◽

10.1182/blood-2014-10-606830 ◽

2015 ◽

Vol 125 (20) ◽

pp. 3183-3192 ◽

Cited By ~ 84

Author(s):

Dawn K. Reichenbach ◽

Vincent Schwarze ◽

Benjamin M. Matta ◽

Victor Tkachev ◽

Elisabeth Lieberknecht ◽

...

Keyword(s):

T Cell ◽

Inflammatory Cytokines ◽

T Cell Activation ◽

Cell Activation ◽

Acute Gvhd ◽

Negative Regulator ◽

Effector T Cell ◽

Cell Responses ◽

Key Points ◽

Pro Inflammatory Cytokines

Key Points IL-33 and ST2 expression are increased post-conditioning and with GVHD, resulting in increased T-cell activation via the IL-33/ST2 axis. Infusion of ST2-Fc protein exploits sST2’s function as a negative regulator of acute GVHD inhibiting pro-inflammatory cytokines.

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