Liver Resection Promotes (Regulates) Proinflammatory Cytokines in Patients with Hepatocellular Carcinoma

Background. Several animal studies have shown the roles of cytokines in regulating liver regeneration following liver resection (LR), which is a type of surgery designed to remove cancerous tumors from the liver. This study investigated how the expressions and serum levels of some pro- and anti-inflammatory cytokines in patients with hepatocellular carcinoma (HCC) were changed during LR. Methods. Liver tissues from 15 patients with HCC were collected and the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), IL-1α, IL-1 β, IL-10, and transforming growth factor-beta1 (TGF-β1) were assessed using real-time PCR assay at different times before and after LR. The serum values of TNF-α and IL-6 were also measured by ELISA. Results. After 60 and 90 minutes of LR, IL-6 gene expression was significantly increased P < 0.001 − 0.05 . The same trend was also observed in TNF-α expression after 90 minutes of LR P < 0.01 . No significant changes were observed in the expressions of IL-1α, IL-1β, IL-10, and TGF-β1 before and after LR. In addition, LR had significant effects on TNF-α and IL-6 serum levels P < 0.05 − 0.0001 . Conclusion. Our data provided further evidence to reveal that IL-6 and TNF-α cytokines are critical to improve liver regeneration.

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Liver resection promotes (regulates) pro-inflammatory cytokines in patients with hepatocellular carcinoma

10.21203/rs.3.rs-362852/v1 ◽

2021 ◽

Author(s):

Farshid Fathi ◽

Behnam Sanei ◽

Mazdak Ganjalikhani Hakemi ◽

Reza F. Saidi ◽

Abbass Rezaei

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Resection ◽

Liver Regeneration ◽

Inflammatory Cytokines ◽

Animal Studies ◽

Transforming Growth Factor ◽

Serum Levels ◽

Tnf Α ◽

Before And After ◽

Tgf Β1

Abstract Objective: Several animal studies have shown the roles of cytokines in regulating liver regeneration following liver resection (LR), which is a type of surgery is designed to remove cancerous tumors from liver. This study investigated how the expressions and serum levels of some pro- and anti-inflammatory cytokines in patients with hepatocellular carcinoma (HCC) were changed during LR.Liver tissues from 15 patients with HCC were collected and the levels of interleukin-6 (IL-6), tumornecrosis factor-alpha (TNF-α), IL-1α, IL-1 β, IL-10, and transforming growth factor- beta1 (TGF-β1) were assessed using real-time PCR assay at different times before and after LR. The serum values of TNF-α and IL-6 were also measured by ELISA.Results: After 60 and 90 minutes of LR, IL-6 gene expression was significantly increased (P < 0.001-0.05). The same trend was also observed in TNF-α expression after 90 minutes of LR (P <0.01). No significant changes were observed in the expressions of IL-1α, IL-1β, IL-10, and TGF-β1 before and after LR. In addition, LR had significant effects on TNF-α and IL-6 serum levels (P<0.05-0.0001). Our data provided further evidence to reveal that IL-6 and TNF-α cytokines are critical to improve liver regeneration.

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The Possible Protective Effect of Selenium on Liver Dysfunction in a Rat Model of Extrahepatic Cholestasis

QJM ◽

10.1093/qjmed/hcab117.002 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Fatma M Lebda ◽

Sahar M El Agaty ◽

Noha A Nassef ◽

Marina A Aziz

Keyword(s):

Bile Duct ◽

Transforming Growth Factor ◽

Group Versus ◽

Serum Levels ◽

Selenium Supplementation ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Tgf Β1 ◽

Necrosis Factor

Abstract Background Oxidative stress and inflammation are primarily implicated in the development and progression of liver injury during cholestasis. Selenium, a known essential antioxidant trace element, was found to provide a remarkable antioxidant and anti-inflammatory effects on various diseases. Aim This study was planned to evaluate the possible protective effect of selenium supplementation in a rat model of chronic cholestasis. Design Experimental study. Methods This study was carried out on adult male rats allocated randomly into sham, bile duct ligated (BDL), and BDL-selenium treated (BDL-Se) groups. Sodium selenite was given by gavage daily, in a dose of 100 µg/kg for 6 weeks, starting 2 weeks before the BDL. Results BDL group presented a significant increase in serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and liver levels of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1(TGF-β1), associated with a significant decrease in serum levels of total proteins (TP) compared to sham group . Selenium supplementation significantly lowered serum levels of AST, ALT, ALP, and liver levels of MDA, TNF-α, and TGF-β1 along with a significant increase in serum TP in BDL-Se group versus BDL rats. Histological analysis of liver showed a significant attenuation of the inflammatory score and a significant decrease in the percentage area of collagen deposition in BDL-Se group versus BDL rats. Conclusion Selenium supplementation reduces liver injury and improves liver functions in experimental cholestasis probably by its antioxidant and anti-inflammatory activities, which further alleviate the liver fibrosis. Abbreviations BDL: bile duct ligated group, BDL-Se: bile duct ligated-selenium group, MDA: malondialdehyde, TNF-α: tumour necrosis factor-alpha, TGF-β1: transforming growth factor- beta1, ROS: reactive oxygen species, mRNA: messenger RNA, IL-6: interleukin-6, BW: body weight, AST: aspartate aminotransferase, ALT: alanine aminotransferase, ALP: alkaline phosphatase, TP: total proteins, CCl4: carbon tetrachloride, GPx: glutathione peroxidase enzyme, SOD: superoxide dismutase, IL-1: interleukin-1.

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Angiography significantly decreased serum levels of IL-8 independent of artery stenosis

10.21203/rs.3.rs-119094/v1 ◽

2020 ◽

Author(s):

Lida Zare ◽

Akram Eidi ◽

Mohammad Safarian ◽

Mohammad Kazemi Arababadi

Keyword(s):

Protective Factor ◽

Serum Levels ◽

Artery Stenosis ◽

Enzyme Linked Immunosorbent Assay ◽

Dependent Manner ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Before And After ◽

Elisa Technique ◽

Factor Alpha

Abstract Background Angiography is a safe cardiovascular technique for the diagnosis and treatment of the cardiovascular disorders. The potential effects of angiography on the cytokines are yet to be clarified completely. Interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) are the important pro-inflammatory cytokines that participate in the pathogenesis of artery stenosis. The aim of his project was to study the angiography effects on the serum levels of IL-8 and TNF-α. Methods Fifty-five participants in three groups, without, with one and with more than one artery stenosis, were explored in this project. Serum levels of IL-8 and TNF-α were measured in the participants before and after angiography using enzyme linked immunosorbent assay (ELISA) technique. Results Serum levels of IL-8, but not TNF-α, were significantly decreased following angiography. X-ray doses had moderate positive correlation with serum levels of TNF-α in the patients with more than one artery stenosis. Serum levels of IL-8 and TNF-α were not different among male and female participants in all groups. Discussion Angiography may be a protective factor for inflammation in IL-8 dependent manner. Using angiography in the patients with more than one artery stenosis needs to be executed cautiously.

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Effect of intestinal colonisation by two Lactobacillus strains on the immune response of gnotobiotic mice

Beneficial Microbes ◽

10.3920/bm2013.0075 ◽

2014 ◽

Vol 5 (4) ◽

pp. 409-419 ◽

Cited By ~ 9

Author(s):

R.S. Steinberg ◽

M. Lima ◽

N.L. Gomes de Oliveira ◽

A. Miyoshi ◽

J.R. Nicoli ◽

...

Keyword(s):

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Quantitative Polymerase Chain Reaction ◽

Necrosis Factor Alpha ◽

Interleukin 5 ◽

Germ Free ◽

Intestinal Colonisation ◽

Tnf Α ◽

Tgf Β1 ◽

Intragastric Gavage

The effect of intestinal colonisation on the immune system was investigated in germ-free mice monoassociated with Lactobacillus strains isolated from calf faeces. Single doses of Lactobacillus acidophilus L36 or Lactobacillus salivarius L38 were administered to germ-free mice by intragastric gavage. Ten days later, the mice were euthanised. Gene expression levels of interleukin 5 (IL-5), IL-6, IL-10, IL-12b, IL-17a, gamma interferon (IFN-γ), transforming growth factor beta 1 (TGF-β1), and tumour necrosis factor alpha (TNF-α) were quantified in segments of the small and large intestines by real time quantitative polymerase chain reaction. All the mice were colonised rapidly after Lactobacillus administration with intestinal counts ranging from 6.53 to 8.26 log cfu/g. L. acidophilus L36 administration increased the expression of cytokines involved with the Th2 (IL-5, IL-6 and TGF-β1) and Th17 (IL-17a, TNF-α and IL-6) inflammatory response, whereas L. salivarius L38 appeared to stimulate a pattern of less diversified cytokines in the intestine. Intragastric gavage of L. acidophilus L36 and L. salivarius L38 induced similar levels of colonisation in the digestive tracts of germ-free mice but stimulated different immune responses in the intestinal mucosa. The different immunomodulation patterns might facilitate the potential use of these lactobacilli as probiotics to treat distinct pathological conditions, for example protection against Citrobacter rodentium infection by stimulating IL-17 production.

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Altered Cytokine Production and Impaired Antimycobacterial Immunity in Protein-Malnourished Guinea Pigs

Infection and Immunity ◽

10.1128/iai.66.8.3562-3568.1998 ◽

1998 ◽

Vol 66 (8) ◽

pp. 3562-3568 ◽

Cited By ~ 71

Author(s):

Guixiang Dai ◽

David N. McMurray

Keyword(s):

Transforming Growth Factor Beta ◽

Guinea Pigs ◽

Transforming Growth Factor ◽

Serum Levels ◽

Peritoneal Macrophages ◽

Protein Malnutrition ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Cd4 Lymphocytes

ABSTRACT Protein malnutrition leads to multiple detrimental alterations of host immune responses to mycobacterial infection. In this study, we demonstrated that splenocytes from low-protein (LP) guinea pigs vaccinated 6 weeks previously with attenuated Mycobacterium tuberculosis H37Ra failed to control the accumulation of virulentM. tuberculosis H37Rv in cocultured autologous peritoneal macrophages, despite the fact that they were able to control the accumulation of virulent tubercle bacilli in cocultured syngeneic peritoneal macrophages from normally nourished guinea pigs as successfully as did those from high-protein (HP) counterparts. Vaccine-induced growth control of virulent M. tuberculosisH37Rv in these cocultures appeared to be mediated by CD4 lymphocytes but not CD8 cells. Tuberculin (purified protein derivative [PPD])-induced lymphoproliferation was markedly impaired in vaccinated LP guinea pigs, and the depletion of CD4 lymphocytes significantly decreased lymphocyte proliferation whereas CD8 cell depletion did not. Protein malnutrition also impaired the abilities of cells from vaccinated LP guinea pigs to produce cytokines, including interferon, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β), in response to PPD, despite the demonstration of higher serum levels of TNF-α and TGF-β after an intravenous injection of PPD into LP guinea pigs. In contrast, peritoneal macrophages from protein-malnourished guinea pigs produced a higher level of TGF-β 4 days after infection in vitro with M. tuberculosis H37Rv than did those from protein adequate controls. These results suggest that dietary protein malnutrition impairs vaccine-induced resistance to M. tuberculosis, in part, by altering the cytokine profile to favor macrophage deactivation.

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Cytokine Production and Monocyte HLA-DR Expression as Predictors of Outcome for Patients with Community-Acquired Severe Infections

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.11.1.161-167.2004 ◽

2004 ◽

Vol 11 (1) ◽

pp. 161-167 ◽

Cited By ~ 98

Author(s):

A. Lekkou ◽

M. Karakantza ◽

A. Mouzaki ◽

F. Kalfarentzos ◽

C. A. Gogos

Keyword(s):

Severe Sepsis ◽

Transforming Growth Factor ◽

Final Outcome ◽

Necrosis Factor Alpha ◽

Hla Dr ◽

Tnf Α ◽

Severe Infections ◽

Anti Inflammatory ◽

The Impact ◽

Tgf Β1

ABSTRACT This study was performed to evaluate the impact of pro- and anti-inflammatory molecules and human leukocyte antigen DR (HLA-DR) expression as markers of immune status for the final outcome of septic patients. The study included 30 patients with severe sepsis due to community-acquired infections. Concentrations of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8, IL-10, and transforming growth factor β1 (TGF-β1) in serum, as well as monocyte HLA-DR expression, were determined on admission and on days 3, 10, 13, and 17 during hospitalization. Of the 30 patients enrolled, 13 survived, while 17 died during their hospital stay. All patients had significantly lower HLA-DR expression and higher pro- and anti-inflammatory cytokine levels than healthy individuals. HLA-DR expression was significantly decreased in nonsurvivors at almost all time points. In nonsurvivors, higher levels in serum of TNF-α on days 13 and 17; IL-6 levels on day 3; and IL-10 on days 3, 10, and 13 were found. Baseline levels of TGF-β1 were significantly higher in survivors. Independent risk factors of mortality were IL-10 levels on days 3 and 10, while monocyte HLA-DR expression on admission was a good predictor for survival. Several pro- and anti-inflammatory cytokines are oversynthesized during severe infections, especially in patients with a poor outcome. Monocyte HLA-DR expression is an early and constant predictive marker for survival in severe sepsis, while serum IL-10 levels on days 3 and 10 have negative prognostic value for the final outcome.

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Role of endocannabinoid CB1 receptors in Streptozotocin-induced uninephrectomised Wistar rats in diabetic nephropathy

Beni-Suef University Journal of Basic and Applied Sciences ◽

10.1186/s43088-021-00121-y ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Jayarami Reddy Medapati ◽

Deepthi Rapaka ◽

Veera Raghavulu Bitra ◽

Santhosh Kumar Ranajit ◽

Girija Sankar Guntuku ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Morphological Changes ◽

Serum Levels ◽

Cb1 Receptors ◽

Protective Effects ◽

Renal Hypertrophy ◽

Necrosis Factor Alpha

Abstract Background The endocannabinoid CB1 receptor is known to have protective effects in kidney disease. The aim of the present study is to evaluate the potential agonistic and antagonistic actions and to determine the renoprotective potential of CB1 receptors in diabetic nephropathy. The present work investigates the possible role of CB1 receptors in the pathogenesis of diabetes-induced nephropathy. Streptozotocin (STZ) (55 mg/kg, i.p., once) is administered to uninephrectomised rats for induction of experimental diabetes mellitus. The CB1 agonist (oleamide) and CB1 antagonist (AM6545) treatment were initiated in diabetic rats after 1 week of STZ administration and were given for 24 weeks. Results The progress in diabetic nephropathy is estimated biochemically by measuring serum creatinine (1.28±0.03) (p < 0.005), blood urea nitrogen (67.6± 2.10) (p < 0.001), urinary microprotein (74.62± 3.47) (p < 0.005) and urinary albuminuria (28.31±1.17) (p < 0.0001). Renal inflammation was assessed by estimating serum levels of tumor necrosis factor alpha (75.69±1.51) (p < 0.001) and transforming growth factor beta (8.73±0.31) (p < 0.001). Renal morphological changes were assessed by estimating renal hypertrophy (7.38± 0.26) (p < 0.005) and renal collagen content (10.42± 0.48) (p < 0.001). Conclusions From the above findings, it can be said that diabetes-induced nephropathy may be associated with overexpression of CB1 receptors and blockade of CB1 receptors might be beneficial in ameliorating the diabetes-induced nephropathy. Graphical abstract

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Alterations of serum levels of plasminogen, TNF-α, and IDO in granulomatosis with polyangiitis patients

Vascular ◽

10.1177/1708538120986305 ◽

2021 ◽

pp. 170853812098630

Author(s):

Dobroslav Kyurkchiev ◽

Tsvetelina Yoneva ◽

Adelina Yordanova ◽

Ekaterina Kurteva ◽

Georgi Vasilev ◽

...

Keyword(s):

Granulomatosis With Polyangiitis ◽

Renal Involvement ◽

Clinical Manifestations ◽

Area Under The Curve ◽

Serum Levels ◽

Necrosis Factor Alpha ◽

Cross Sectional ◽

Spearman's Rho ◽

Tnf Α ◽

Spearman’S Rho

Background Granulomatosis with polyangiitis (GPA) is a representative of vasculitides associated with anti-neutrophil cytoplasmic autoantibodies. “Classical” antibodies directed against proteinase 3 are involved in the pathogenesis and are part of the GPA diagnosis at the same time. Along with them, however, antibodies against Lysosomal-Associated Membrane Protein-2 (LAMP-2) and antibodies directed against plasminogen have been described in GPA. Objectives and methodology: We performed a cross-sectional study enrolling 34 patients diagnosed with GPA. Our study was aimed at looking for correlations between serum levels of LAMP-2 and plasminogen and the clinical manifestations of the GPA. Furthermore, we examined serum levels of tumor necrosis factor-alpha (TNF-α) and its associated indoleamine-pyrrole 2,3-dioxygenase (IDO), as well as we looked for a correlation between these cytokines and the clinical manifestations of GPA. Results The results showed that in GPA, serum plasminogen levels were negatively associated with renal involvement (receiver operating characteristic (ROC) area under the curve (AUC) of 0.78) (95% CI 0.53–0.91), p = 0.035, and the extent of proteinuria, Spearman’s Rho = –0.4, p = 0.015. Increased levels of TNF-α and IDO correlated with disease activity, Spearman’s Rho =0.62, p = 0.001 and Spearman’s Rho = 0.4, p = 0.022, respectively, whereas only TNF-α was increased in severe forms of GPA with lung involvement (ROC AUC of 0.8) (95% CI 0.66–0.94), p = 0.005. Conclusions In this study, we demonstrate the alteration of soluble factors, which play an important role in the pathogenesis of GPA and their relationship with the clinical manifestations of the disease. Our main results confirm the associations of increased secretory TNF-α and some clinical manifestations, and we describe for the first time decreased serum plasminogen levels and their association with renal involvement.

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Attenuation of diethyl nitrosamine-induced hepatocellular carcinoma by taxifolin and/or alogliptin: The interplay between toll-like receptor 4, transforming growth factor beta-1, and apoptosis

Human & Experimental Toxicology ◽

10.1177/09603271211008496 ◽

2021 ◽

pp. 096032712110084

Author(s):

AM Kabel ◽

HH Arab ◽

MA Abd Elmaaboud

Keyword(s):

Hepatocellular Carcinoma ◽

Transforming Growth Factor Beta ◽

Caspase 3 ◽

Transforming Growth Factor ◽

Liver Function Tests ◽

Toll Like Receptor ◽

Caspase 9 ◽

Toll Like Receptor 4 ◽

Growth Factor Beta ◽

Tgf Β1

Hepatocellular carcinoma (HCC) is the most common form of liver malignancies worldwide. Alogliptin is an anti-diabetic that may have effective anticancer properties against many types of malignancies. Taxifolin is a flavonoid that has potent antioxidant, and anti-inflammatory properties. The objective of this study was to explore the impact of alogliptin and/or taxifolin on diethyl nitrosamine-induced HCC in rats. One hundred male Wistar rats were divided into five equal groups as follows: Control; HCC; HCC + Alogliptin; HCC + Taxifolin; and HCC + Alogliptin + Taxifolin group. The survival rate, liver function tests, tissue antioxidant enzymes, malondialdehyde (MDA), nuclear factor (erythroid derived 2)-like 2 (Nrf2), transforming growth factor beta 1 (TGF-β1), interleukin 1 alpha (IL-1α), and toll-like receptor 4 (TLR4) were measured. Also, hepatic caspase 3, caspase 9, beclin-1, and c-Jun NH2-terminal kinase (JNK) in addition to serum alpha-fetoprotein (AFP) and α-L-Fucosidase (AFU) were assessed. Specimens of the liver were subjected to histopathological examination. Alogliptin and/or taxifolin induced significant improvement of liver function tests with significant increase in the survival rate, tissue antioxidant enzymes, Nrf2, caspase 3, caspase 9, Beclin-1 and JNK activities associated with significant decrease in serum AFP and AFU, tissue MDA, TGF-β1, IL-1α and TLR4 expression compared to HCC group. These results were significant with taxifolin/alogliptin combination when compared to the use of each of these agents alone. In conclusion, taxifolin/alogliptin combination might be used as adjuvant therapy for attenuation of HCC.

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Regulation of extracellular matrix synthesis by TNF-α and TGF-β1 in type II cells exposed to coal dust

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1998.275.4.l637 ◽

1998 ◽

Vol 275 (4) ◽

pp. L637-L644 ◽

Cited By ~ 3

Author(s):

Yu-Chen Lee ◽

D. Eugene Rannels

Keyword(s):

Extracellular Matrix ◽

Cell Cultures ◽

Transforming Growth Factor ◽

Coal Dust ◽

Transforming Growth Factor Β1 ◽

Type Ii ◽

Tnf Α ◽

Type Ii Cell ◽

Primary Type ◽

Tgf Β1

Type II pulmonary epithelial cells respond to anthracite coal dust PSOC 867 with increased synthesis of extracellular matrix (ECM) components. Alveolar macrophages modulate this response by pathways that may involve soluble mediators, including tumor necrosis factor-α (TNF-α) or transforming growth factor-β1 (TGF-β1). The effects of TNF-α (10 ng/ml) and/or TGF-β1 (2 ng/ml) were thus investigated in dust-exposed primary type II cell cultures. In control day 1 or day 3 cultures, TNF-α and/or TGF-β1 had little or no effect on the synthesis of type II cellular proteins, independent of whether the cells were exposed to dust. With PSOC 867 exposure, where ECM protein synthesis is elevated, TNF-α and TGF-β1 further increased both the absolute and relative rates of ECM synthesis on day 3 but had little effect on day 1. Each mediator increased expression of fibronectin mRNA, as well as of ECM fibronectin content, in a manner qualitatively similar to their effects on synthesis. Thus TNF-α and TGF-β1 modulate both ECM synthesis and fibronectin content in coal dust-exposed type II cell cultures.

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