scholarly journals Effect of Clinoptilolite and Sepiolite Nanoclays on Human and Parasitic Highly Phagocytic Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Yanis Toledano-Magaña ◽  
Leticia Flores-Santos ◽  
Georgina Montes de Oca ◽  
Alfonso González-Montiel ◽  
Juan-Pedro Laclette ◽  
...  
Keyword(s):  
Cell Line ◽  
Human Peripheral Blood ◽  
Dependent Manner ◽  
Blood Monocytes ◽  
Phagocytic Cells ◽  
Need To Evaluate ◽  
Potential Applications ◽  
Low Cytotoxicity ◽  
Dose Dependent

Nanoclays have potential applications in biomedicine raising the need to evaluate their toxicity inin vitromodels as a first approach to its biocompatibility. In this study,in vitrotoxicity of clinoptilolite and sepiolite nanoclays (NC) was analyzed in highly phagocytic cultures of amoebas and human and mice macrophages. While amebic viability was significantly affected only by sepiolite NC at concentrations higher than 0.1 mg/mL, the effect on macrophage cultures was dependent on the origin of the cells. Macrophages derived from human peripheral blood monocytes were less affected in viability (25% decrease at 48 h), followed by the RAW 264.7 cell line (40%), and finally, macrophages derived from mice bone marrow monocytes (98%). Moreover, the cell line and mice macrophages die mainly by necrosis, whereas human macrophages exhibit increased apoptosis. Cytokine expression analysis in media of sepiolite NC treated cultures showed a proinflammatory profile (INFγ, IL-1α, IL-8, and IL-6), in contrast with clinoptilolite NC that induced lees cytokines with concomitant production of IL-10. The results show that sepiolite NC is more toxic to amoebas and macrophages than clinoptilolite NC, mostly in a time and dose-dependent manner. However, the effect of sepiolite NC was comparable with talc powder suggesting that both NC have low cytotoxicityin vitro.

scholarly journals Streptococcus pneumoniae Autolysis Prevents Phagocytosis and Production of Phagocyte-Activating Cytokines

2009 ◽  
Vol 77 (9) ◽  
pp. 3826-3837 ◽  
Author(s):  
Anna Martner ◽  
Susann Skovbjerg ◽  
James C. Paton ◽  
Agnes E. Wold
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 12 ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Exact Function ◽  
Ifn Γ ◽  
Dose Dependent

ABSTRACT Streptococcus pneumoniae is a major pathogen in humans. The pathogenicity of this organism is related to its many virulence factors, the most important of which is the thick pneumococcal capsule that minimizes phagocytosis. Another virulence-associated trait is the tendency of this bacterium to undergo autolysis in stationary phase through activation of the cell wall-bound amidase LytA, which breaks down peptidoglycan. The exact function of autolysis in pneumococcal pathogenesis is, however, unclear. Here, we show the selective and specific inefficiency of wild-type S. pneumoniae for inducing production of phagocyte-activating cytokines in human peripheral blood mononuclear cells (PBMC). Indeed, clinical pneumococcal strains induced production of 30-fold less tumor necrosis factor (TNF), 15-fold less gamma interferon (IFN-γ), and only negligible amounts of interleukin-12 (IL-12) compared with other closely related Streptococcus species, whereas the levels of induction of IL-6, IL-8, and IL-10 production were similar. If pneumococcal LytA was inactivated by mutation or by culture in a medium containing excess choline, the pneumococci induced production of significantly more TNF, IFN-γ, and IL-12 in PBMC, whereas the production of IL-6, IL-8, and IL-10 was unaffected. Further, adding autolyzed pneumococci to intact bacteria inhibited production of TNF, IFN-γ, and IL-12 in a dose-dependent manner but did not inhibit production of IL-6, IL-8, and IL-10 in response to the intact bacteria. Fragments from autolyzed bacteria inhibited phagocytosis of intact bacteria and reduced the in vitro elimination of pneumococci from human blood. Our results suggest that fragments generated by autolysis of bacteria with reduced viability interfere with phagocyte-mediated elimination of live pneumococci.

scholarly journals Leukotriene B4 stimulates c-fos and c-jun gene transcription and AP-1 binding activity in human monocytes

1992 ◽  
Vol 282 (3) ◽  
pp. 625-629 ◽  
Author(s):  
J Staňková ◽  
M Rola-Pleszczynski
Keyword(s):  
Human Peripheral Blood ◽  
Leukotriene B4 ◽  
Binding Activity ◽  
Dependent Manner ◽  
Blood Monocytes ◽  
Concentration Dependent Manner ◽  
Nuclear Factors ◽  
Oncogene Products ◽  
Kinetics Of

We have examined the effect of leukotriene B4 (LTB4), a potent lipid proinflammatory mediator, on the expression of the proto-oncogenes c-jun and c-fos. In addition, we looked at the modulation of nuclear factors binding specifically to the AP-1 element after LTB4 stimulation. LTB4 increased the expression of the c-fos gene in a time- and concentration-dependent manner. The c-jun mRNA, which is constitutively expressed in human peripheral-blood monocytes at relatively high levels, was also slightly augmented by LTB4, although to a much lower extent than c-fos. The kinetics of expression of the two genes were also slightly different, with c-fos mRNA reaching a peak at 15 min after stimulation and c-jun at 30 min. Both messages rapidly declined thereafter. Stability of the c-fos and c-jun mRNA was not affected by LTB4, as assessed after actinomycin D treatment. Nuclear transcription studies in vitro showed that LTB4 increased the transcription of the c-fos gene 7-fold and the c-jun gene 1.4-fold. Resting monocytes contained nuclear factors binding to the AP-1 element, but stimulation of monocytes with LTB4 induced greater AP-1-binding activity of nuclear proteins. These results indicate that LTB4 may regulate the production of different cytokines by modulating the yield and/or the function of transcription factors such as AP-1-binding proto-oncogene products.

scholarly journals Thiols decrease human interleukin (IL) 4 production and IL-4-induced immunoglobulin synthesis.

1995 ◽  
Vol 182 (6) ◽  
pp. 1785-1792 ◽  
Author(s):  
P Jeannin ◽  
Y Delneste ◽  
S Lecoanet-Henchoz ◽  
J F Gauchat ◽  
P Life ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Messenger Rna ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Dependent Manner ◽  
Dose Dependent

N-Acetyl-L-cysteine (NAC) is an antioxidant precursor of intracellular glutathione (GSH), usually given in human as a mucolytic agent. In vitro, NAC and GSH have been shown to act on T cells by increasing interleukin (IL) 2 production, synthesis and turnover of IL-2 receptors, proliferation, cytotoxic properties, and resistance to apoptosis. We report here that NAC and GSH decrease in a dose-dependent manner human IL-4 production by stimulated peripheral blood T cells and by T helper (Th) 0- and Th2-like T cell clones. This effect was associated with a decrease in IL-4 messenger RNA transcription. In contrast, NAC and GSH had no effect on interferon gamma and increased IL-2 production and T cell proliferation. A functional consequence was the capacity of NAC and GSH to selectively decrease in a dose-dependent manner IL-4-induced immunoglobulin (Ig) E and IgG4 production by human peripheral blood mononuclear cells. Interestingly, NAC and GSH also acted directly on purified tonsillar B cells by decreasing the mature epsilon messenger RNA, hence decreasing IgE production. In contrast, IgA and IgM production were not affected. At the same time, B cell proliferation was increased in a dose-dependent manner. Not all antioxidants tested but only SH-bearing molecules mimicked these properties. Finally, when given orally to mice, NAC decreased both IgE and IgG1 antibody responses to ovalbumin. These results demonstrate that NAC, GSH, and other thiols may control the production of both the Th2-derived cytokine IL-4 and IL-4-induced Ig in vitro and in vivo.

scholarly journals Differentiation stimuli induce receptors for plasma fibronectin on the human myelomonocytic cell line HL-60

Blood ◽  
1984 ◽  
Vol 64 (4) ◽  
pp. 858-866
Author(s):  
CG Pommier ◽  
J O'Shea ◽  
T Chused ◽  
T Takahashi ◽  
M Ochoa ◽  
...  
Keyword(s):  
Cell Line ◽  
Human Peripheral Blood ◽  
Cell Types ◽  
Plasma Fibronectin ◽  
Blood Monocytes ◽  
Before And After ◽  
Differentiating Agents ◽  
Membrane Antigens ◽  
Human Polymorphonuclear Leukocytes

Plasma fibronectin (Fn) induces phagocytosis of C3b-opsonized sheep erythrocytes (EC3b) by human peripheral blood monocytes. However, Fn does not induce erythrophagocytosis of EC3b by human polymorphonuclear leukocytes (PMN), unless the PMN have been exposed to C5a or N-formyl- methionyl-leucyl-phenylalanine. Because of this difference, it is of great interest to examine Fn binding to cells that possess the capacity to differentiate into either granulocytes or monocytes. Hence, we have examined the consequences of Fn binding to the human myelomonocytic cell line, HL-60, both before and after in vitro differentiation of the HL-60, along a monocytoid or a granulocytoid pathway. Fn receptors were not found on undifferentiated HL-60, but several differentiating agents promoted the HL-60 binding of Fn-coated microspheres (Fn-ms). The peak of Fn-ms binding occurred four to five days after the induction of differentiation with dimethylsulfoxide (DMSO), and two days after induction by PMA. In addition, cells that differentiated along either the monocytoid or the granulocytoid pathway showed a marked increase in the phagocytosis of both IgG-coated erythrocytes (EA) and EC3b when they were exposed to Fn. Comparison of the effects of anti-Fn monoclonals on the binding of Fn-ms to the monocytes, PMN, and HL-60 showed that the same monoclonals block Fn-ms-binding and Fn-induced EC3b phagocytosis by all three cell types. Two monoclonal antibodies, M1/70 and A6F10, directed against membrane antigens on PMN and monocytes, inhibited Fn-ms binding. Both also blocked Fn-induced EC3b ingestion by these cells. However, neither antibody blocked Fn-ms binding or EC3b ingestion by differentiated HL-60. We conclude that differentiated HL-60 cells express functionally active Fn receptors, similar to monocytes and activated PMN, which, nonetheless, differ from normal cells in their association with the antigens recognized by M1/70 and A6F10.

In Vitro Activity of a Novel Fully Human Anti-CD40 Antibody CHIR-12.12 in Chronic Lymphocytic Leukemia: Blockade of CD40 Activation and Induction of ADCC.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2504-2504 ◽  
Author(s):  
Xia Tong ◽  
Georgios V. Georgakis ◽  
Long Li ◽  
O’Brien Susan ◽  
Younes Anas ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cell Death ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Line ◽  
Blood Donors ◽  
Lymphocytic Leukemia ◽  
Dependent Manner ◽  
Dose Dependent

Abstract B-cell chronic lymphocytic leukemia (CLL) is characterized by in vivo accumulation of long-lived CD5+ B cells. However when cultured in vitro CLL cells die quickly by apoptosis. Protection from apoptosis in vivo is believed to result from supply of survival signals provided by cells in the microenvironment. We and others have previously reported that CLL cells express CD40 receptor, and that CD40 stimulation of CLL cells may rescue CLL cells from spontaneous and drug-induced apoptosis in vitro. These observations suggested that blocking CD40-CD40L pathway might deprive CLL cells from survival signals and induce apoptosis. To test this hypothesis, we have generated a fully human anti-CD40 blocking monoclonal antibody in XenoMousemice (Abgenix, Inc.). The antibody CHIR-12.12 was first evaluated for its effect on normal human lymphocytes. Lymphocytes from all 10 healthy blood donors did not proliferate in response to CHIR-12.12 at any concentration tested (0.0001 mg/ml to 10 mg/ml range). In contrast, activating CD40 on normal B-lymphocytes by CD40L induced their proliferation in vitro. Importantly, CHIR-12.12 inhibited CD40L- induced proliferation in a dose dependent manner with an average IC50 of 51 ± 26 pM (n=10 blood donors). The antagonistic activity of CHIR-12.12 was then tested in primary CLL samples from 9 patients. CHIR-12.12 alone did not induce CLL cell proliferation. In contrast, primary CLL cells incubated with CD40L, either resisted spontaneous cell death or proliferated. This effect was reversed by co-incubation with CHIR-12.12 antibody, restoring CLL cell death (n=9). CHIR-12.12 was then examined for its ability to lyse CLL cell line EHEB by antibody dependent cell mediated cytotoxicity (ADCC). Freshly isolated human NK cells from normal volunteer blood donors were used as effector cells. CHIR-12.12 showed lysis activity in a dose dependent manner and produced maximum lysis levels at 0.1 mg/ml. When compared with rituximab, CHIR-12.12 mediated greater maximum specific lysis (27.2 % Vs 16.2 %, p= 0.007). The greater ADCC by CHIR-12.12 was not due to higher density of CD40 molecules on CLL cell line compared to CD20 molecules. The CLL target cells expressed 509053 ±13560 CD20 molecules compared to 48416 ± 584 CD40 molecules. Collectively, these preclinical data suggest that CHIR-12.12 monoclonal antibody may have a therapeutic role in patients with CLL.

scholarly journals In vitro differentiation of human monocytes. Differences in monocyte phenotypes induced by cultivation on glass or on collagen.

1982 ◽  
Vol 156 (4) ◽  
pp. 1101-1114 ◽  
Author(s):  
G Kaplan ◽  
G Gaudernack
Keyword(s):  
Human Peripheral Blood ◽  
Surface Antigens ◽  
Fc Receptor ◽  
Mononuclear Phagocytes ◽  
Receptor Expression ◽  
Blood Monocytes ◽  
In Vitro Differentiation ◽  
Phagocytic Cells ◽  
Stage Of Development

We demonstrated that the in vitro differentiation of human peripheral blood monocytes to macrophages is dependent on the environment and conditions of monocyte culture. Cultivation of monocytes on glass or microexudate-coated glass gave rise to cells resembling foreign body granuloma macrophages. After an initial rise in Fc receptor- and C3 receptor-mediated phagocytosis, a progressive loss of Fc receptor expression and C3-mediated ingestion were observed. The monocyte surface antigens recognized by the anti-human monocyte monoclonal antibodies 1D5 and 63D3 were lost from the surface of the majority of cells cultured on glass and microexudates. A subpopulation of Fc receptor-positive cells that were 1D5 and 63D3 positive was retained in fully differentiated cell populations. In comparison, monocytes cultivated on collagen matrices gave rise to highly phagocytic cells resembling human resident tissue macrophages. Both Fc- and C3-mediated phagocytosis were enhanced and remained so during the entire length of culture. The surface antigens recognized by the 1D5 antibody, expressed on all freshly seeded monocytes, was maintained on the macrophages. The antigen recognized by the 63D3 antibody was not expressed on mature cells. The present evidence would indicate that variations in expression of phagocytic receptors and the surface antigens 1D5 and 63D3 can be ascribed to the stage of development of the macrophage or its stage of activation, rather than to independent subsets of mononuclear phagocytes.

Si-Jun-Zi-Tang Regulate Granulocyte Macrophage Colony-stimulating Factor Secretion by Human Peripheral Blood Mononuclear Cells

1996 ◽  
Vol 24 (01) ◽  
pp. 45-52 ◽  
Author(s):  
Jerming Tseng ◽  
Tsui-Li Li
Keyword(s):  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Suppressive Effect ◽  
Dependent Manner ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Dose Dependent ◽  
Stimulating Factor

Si-Jun-Zi-Tang is one of the widely used Chinese herbal medicines. In this study, human peripheral blood monocytes were treated in vitro with 50% hot ethanol extract of Si-Jun-Zi-Tang and its four major ingredients (Dangshen, Baizhu, Gancao and Fuling). The concentration of granulocyte-macrophage colony-stimulating factor (GM-CSP) in the culture supernatant at 3 hours and 18 hours were measured using an ELISA. Dangshen and Gancao significantly suppressed GM-CSP secretion in a dose-dependent manner. Baizhu showed no statistically significant effect on GM-CSP secretion 18 hours after in vitro drug-treatment. Fuling, by contrast, significantly augmented GM-CSP secretion in a dose dependent manner after 18 hours of drug treatment. Si-Jun-Zi-Tang showed a suppressive effect on GM-CSP secretion at 3 hours but significantly augmented GM-CSP secretion when the cells were treated with 8 mg/ml of the drug for 18 hours. The data suggested that Si-Jun-Zi-Tang might modulate hematopoiesis and immune response via regulating GM-CSP secretion, and the presence of Fuling in Si-Jun-Zi-Tang could counteract the suppressive effect of Dangshen and Gancao on GM-CSP secretion.

scholarly journals Differentiation stimuli induce receptors for plasma fibronectin on the human myelomonocytic cell line HL-60

Blood ◽  
1984 ◽  
Vol 64 (4) ◽  
pp. 858-866 ◽  
Author(s):  
CG Pommier ◽  
J O'Shea ◽  
T Chused ◽  
T Takahashi ◽  
M Ochoa ◽  
...  
Keyword(s):  
Cell Line ◽  
Human Peripheral Blood ◽  
Cell Types ◽  
Plasma Fibronectin ◽  
Blood Monocytes ◽  
Before And After ◽  
Differentiating Agents ◽  
Membrane Antigens ◽  
Human Polymorphonuclear Leukocytes

Abstract Plasma fibronectin (Fn) induces phagocytosis of C3b-opsonized sheep erythrocytes (EC3b) by human peripheral blood monocytes. However, Fn does not induce erythrophagocytosis of EC3b by human polymorphonuclear leukocytes (PMN), unless the PMN have been exposed to C5a or N-formyl- methionyl-leucyl-phenylalanine. Because of this difference, it is of great interest to examine Fn binding to cells that possess the capacity to differentiate into either granulocytes or monocytes. Hence, we have examined the consequences of Fn binding to the human myelomonocytic cell line, HL-60, both before and after in vitro differentiation of the HL-60, along a monocytoid or a granulocytoid pathway. Fn receptors were not found on undifferentiated HL-60, but several differentiating agents promoted the HL-60 binding of Fn-coated microspheres (Fn-ms). The peak of Fn-ms binding occurred four to five days after the induction of differentiation with dimethylsulfoxide (DMSO), and two days after induction by PMA. In addition, cells that differentiated along either the monocytoid or the granulocytoid pathway showed a marked increase in the phagocytosis of both IgG-coated erythrocytes (EA) and EC3b when they were exposed to Fn. Comparison of the effects of anti-Fn monoclonals on the binding of Fn-ms to the monocytes, PMN, and HL-60 showed that the same monoclonals block Fn-ms-binding and Fn-induced EC3b phagocytosis by all three cell types. Two monoclonal antibodies, M1/70 and A6F10, directed against membrane antigens on PMN and monocytes, inhibited Fn-ms binding. Both also blocked Fn-induced EC3b ingestion by these cells. However, neither antibody blocked Fn-ms binding or EC3b ingestion by differentiated HL-60. We conclude that differentiated HL-60 cells express functionally active Fn receptors, similar to monocytes and activated PMN, which, nonetheless, differ from normal cells in their association with the antigens recognized by M1/70 and A6F10.

An Orally Bioavailable Inhibitor of FLT3 and Syk Kinases Prevents Tumor Growth in Subcutaneously Implanted Human Tumor Xenografts and Promotes Cell Death of FLT3 Mutant AML Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 243-243 ◽  
Author(s):  
Polly R. Pine ◽  
Rena Bahjat ◽  
Betty Chang ◽  
Vanessa Taylor ◽  
Vadim Markovstov ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Growth ◽  
Cell Line ◽  
Mutant Cell ◽  
Dependent Manner ◽  
Tumor Xenografts ◽  
Orally Bioavailable ◽  
Dose Dependent

Abstract Background. Phase 1 clinical studies have shown that an orally bioavailable syk kinase inhibitor, R788/406, is very well tolerated in human volunteers for up to 7 days (and in primates for up to 28 days) at doses achieving concentrations in excess of 5 micromolar (ED50 for in vivo biomarker of syk-inhibition in humans is 1 micromolar). In biochemical kinase assays, R788/406 inhibits syk and FLT3 at less than 10 nM, and in cell-based assays at less than 100 nM. The demonstration of biological activity and excellent tolerability in humans, and the equipotent inhibition of FLT3 and syk kinases in biochemical assays led us to explore the potential for use of R788/406 in a xenograft of a human AML FLT-3ITD mutant cell line. Objective: To evaluate the in vitro and in vivo activity of R788/406 in a human AML FLT3-ITD mutant cell line, MV411, a model system for examination of FLT3 mutant AML. Methods: MV411 cells were treated with R788/406 and evaluated for cell viability and markers of apoptosis (Annexin-V/PI and caspase) by FACS. Cell cycle analysis was performed on cells stained with PI. 5 X 106 MV411 cells harvested in logarithmic phase growth were injected with Matrigel SC in NOD/SCID mice. Treatment with R788/406 began when tumors reached a predetermined size (mean volume of 100 mm3) and continued for 26 days. At sacrifice, tumor xenografts were lysed, immunoprecipitated with anti-FLT-3, and probed with anti-phosphotyrosine 4G10 or anti-FLT-3. Results: R788/406 potently and selectively induced dose-dependent cytotoxicity of MV-411 AML cells in vitro with an ED50 of 20nM. Pretreatment of cells with R788/406 promoted dephosphorylation of constitutively active pFLT3, as well as a reduction of pStat5 and pErk1/2 in the FLT3 signaling cascade. Moreover, R788/406 induced cell cycle arrest in the G1 phase and subsequent apoptosis in MV411 cells in a dose-dependent manner. Twice daily administration of R788/406 to NOD/SCID mice bearing SC MV411 tumors reduced tumor growth significantly in a dose dependent manner. When compared to vehicle controls, daily doses of 40 and 80mg/kg R788/406 resulted in 45% and 82% inhibition of mean tumor volumes, respectively. At study termination mean tumor volumes were 686.90 ± 115.56 and 224.45 ± 49.80 for 40 and 80 mg/kg R788/406-treated animals compared to 1255.48 ± 182.94 for vehicle controls with a final %T/C of -0.4 (range of %T/C throughout study was −7.9 to −0.4). During the study, no significant body weight loss was observed in any of the animals in this study. Ex vivo analyses of subcutaneous tumors from MV411 tumor-bearing mice showed that R788/406 completely inhibited constitutive FLT3 activation and downstream signaling events. Conclusions: R788/406 is well tolerated in humans (and primates) at concentrations well in excess of those that inhibit syk in vivo. Given the equipotent inhibition of syk and FLT3, the in vivo activity against human syk, and the xenograft data reported here, R788/406 may be a promising agent for FLT-3 AML.

Chemopreventive and hepatoprotective roles of adiponectin (SULF2 inhibitor) in hepatocelluar carcinoma

2016 ◽  
Vol 397 (3) ◽  
pp. 257-267 ◽  
Author(s):  
Mohammed M.H. Al-Gayyar ◽  
Ahmed Abbas ◽  
Ahmed M. Hamdan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Extracellular Enzyme ◽  
Dependent Manner ◽  
Hepg2 Cell Line ◽  
Tnf Α ◽  
Dose Dependent

Abstract Sulfatase 2 (SULF2) is an extracellular enzyme that catalyzes the removal of 6-O-sulfate groups from the heparan sulfate (HS). As elevated SULF2 activity has been correlated with hepatocellular carcinoma (HCC), this study was conducted to evaluate the chemoprotective and the hepatoprotective roles of adiponectin, as a SULF2 inhibitor, against hepatocellular carcinoma both in vivo and in vitro. HCC was induced in rats using thioacetamide (200 mg/kg). Treated rats received adiponectin (5 μg/kg) once a week. Moreover, human hepatocellular carcinoma (HepG2) cell line was used as an in-vitro model. In both in-vivo and in-vitro models, adiponectin completely blocked HCC-induced SULF2 elevation. The antitumor activity of adiponectin was confirmed by 80% increased the survival rate, 73% reduction in the average number of nodules per nodule-bearing liver and 46% reduction in serum AFP. In addition, adiponectin ameliorated HCC-induced expression of tumor invasion markers, MMP9, syndecan-1 and FGF-2. Moreover, adiponectin attenuated HCC-induced elevation of nfκb and TNF-α levels. Moreover, treatment of HepG2 cell line with adiponectin showed dose-dependent reduction of HepG2 cell viability and elevation of cellular cytotoxicity. Besides, Adiponectin yielded the same results in HepG2 cells in a dose-dependent manner. Adiponectin achieved both hepatoprotective and chemoprotective effects against HCC through blocking of SULF2.

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