scholarly journals Effect of a Histone Deacetylases Inhibitor of IL-18 and TNF-Alpha Secretion in Vitro

2018 ◽  
Vol 6 (2) ◽  
pp. 269-273
Author(s):  
Zlatka Georgieva Dobreva ◽  
Boncho Grigorov Grigorov ◽  
Spaska Angelova Stanilova
Keyword(s):  
Gene Expression ◽  
Histone Deacetylases ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Inactive Protein

BACKGROUND: Interleukin-18 (IL-18) and Tumor Necrosis Factor-alpha (TNF-α) are proinflammatory cytokines that increased the development of Th1 immune response, but have a different type of regulation of the gene expression. Whereas TNF-α has an inducible expression, IL-18 is translated as an inactive protein and required proteolytic cleavage by Casp-1 in inflammasome complexes.AIM: To investigate the effect of the histone deacetylases inhibitor Suberoylanilide Hydroxamic Acid (SAHA) on the gene expression and secretion of both cytokines, IL-18 and TNF-α, according to their contribution to the cancer development and anticancer immunity.METHODS: Isolated peripheral blood mononuclear cells (PBMC) were stimulated with LPS and C3bgp with or without SAHA. Cytokine production was assessed by ELISA at 6 and 24h.RESULTS: IL-18 and TNF-α secretion was significantly increased at 6h and 24h in response to stimulation. TNF-α production from stimulated PBMC was downregulated by SAHA at 6 and 24h. Treatment with SAHA does not inhibit the secretion of IL-18 significantly either at 6 or 24h of stimulation.CONCLUSION: The inhibition of histone deacetylases by SAHA does not influence the inflammasome-dependent production of immunologically active IL-18. In contrast, the production of proinflammatory TNF-α in cultures was mediated by the activity of HDAC class I and class II enzymes.

scholarly journals The Flavonoid Quercetin Inhibits Proinflammatory Cytokine (Tumor Necrosis Factor Alpha) Gene Expression in Normal Peripheral Blood Mononuclear Cells via Modulation of the NF-κβ System

2006 ◽  
Vol 13 (3) ◽  
pp. 319-328 ◽  
Author(s):  
Madhavan P. Nair ◽  
Supriya Mahajan ◽  
Jessica L. Reynolds ◽  
Ravikumar Aalinkeel ◽  
Harikrishnan Nair ◽  
...  
Keyword(s):  
Gene Expression ◽  
Proinflammatory Cytokine ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Cytokine Tumor Necrosis Factor ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

ABSTRACT The flavonoids comprise a large class of low-molecular-weight plant metabolites ubiquitously distributed in food plants. These dietary antioxidants exert significant antitumor, antiallergic, and anti-inflammatory effects. The molecular mechanisms of their biological effects remain to be clearly understood. We investigated the anti-inflammatory potentials of a safe, common dietary flavonoid component, quercetin, for its ability to modulate the production and gene expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) by human peripheral blood mononuclear cells (PBMC). Our results showed that quercetin significantly inhibited TNF-α production and gene expression in a dose-dependent manner. Our results provide direct evidence of the anti-inflammatory effects of quercetin by PBMC, which are mediated by the inhibition of the proinflammatory cytokine TNF-α via modulation of NF-κβ1 and Iκβ.

scholarly journals Diagnostic Implications of Antigen-Induced Gamma Interferon, Nitric Oxide, and Tumor Necrosis Factor Alpha Production by Peripheral Blood Mononuclear Cells from Mycobacterium bovis-Infected Cattle

2003 ◽  
Vol 10 (5) ◽  
pp. 960-966 ◽  
Author(s):  
W. R. Waters ◽  
M. V. Palmer ◽  
D. L. Whipple ◽  
M. P. Carlson ◽  
B. J. Nonnecke
Keyword(s):  
Bovine Tuberculosis ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Infected Cattle ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Bovine tuberculosis in the United States has proven costly to cattle producers as well as to government regulatory agencies. While in vivo responsiveness to mycobacterial antigens is the current standard for the diagnosis of tuberculosis, in vitro assays are gaining acceptance, especially as ancillary or complementary tests. To evaluate in vitro indices of cellular sensitization, antigen-induced gamma interferon (IFN-γ), nitric oxide (NO), and tumor necrosis factor alpha (TNF-α) responses by blood mononuclear cells from Mycobacterium bovis-infected cattle were quantified and compared. Using an aerosol model of infection, two doses of each of two strains of M. bovis (95-1315 and HC-2045T) were used to induce a range of IFN-γ, NO, and TNF-α responses. Infection-specific increases in NO, but not in IFN-γ or TNF-α, were detected in nonstimulated cultures at 48 h, a finding that is indicative of nonspecific activation and spontaneous release of NO. The infective dose of M. bovis organisms also influenced responses. At 34 days postinfection, IFN-γ, NO, and TNF-α responses in antigen-stimulated cells from cattle receiving 105 CFU of M. bovis organisms were greater than responses of cells from cattle infected with 103 CFU of M. bovis organisms. The NO response, but not the IFN-γ and TNF-α responses, was influenced by infective strains of M. bovis. The TNF-α, NO, and IFN-γ responses followed similar kinetics, with strong positive associations among the three readouts. Overall, these findings indicate that NO and TNF-α, like IFN-γ, may prove useful as indices for the diagnosis of bovine tuberculosis.

scholarly journals Immunomodulating Properties of the Antibiotic Novobiocin in Human Monocytes

1998 ◽  
Vol 42 (8) ◽  
pp. 1911-1916 ◽  
Author(s):  
Anja Lührmann ◽  
Jürgen Thölke ◽  
Ingrid Behn ◽  
Jens Schumann ◽  
Gisa Tiegs ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 1 ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Adp Ribosylation ◽  
Surface Molecules ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT We show that the coumeromycin antibiotic novobiocin, a potent inhibitor of ADP ribosylation, prevents lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, and IL-10 secretion in human peripheral blood mononuclear cells. It shares these cytokine-suppressing properties with other inhibitors of ADP ribosylation. We found that novobiocin prevents TNF-α production by inhibiting translation of the TNF-α mRNA. Elevated TNF-α levels in mice treated withd-galactosamine (GalN)-LPS or GalN-TNF were not reduced by novobiocin; however, the drug exhibited hepatoprotective properties. Novobiocin causes downregulation of the surface molecules on monocytes, among which CD14 was the most affected. The diminished expression of surface molecules was not observed on T and B lymphocytes. Similar to other inhibitors of ADP ribosylation, novobiocin prevents LPS-induced phosphate labelling of γ-actins.

scholarly journals Chlamydia pneumoniae-induced tumour necrosis factor alpha responses are lower in children with asthma compared with non-asthma

2018 ◽  
Vol 5 (1) ◽  
pp. e000239 ◽  
Author(s):  
Tamar Anne Smith-Norowitz ◽  
Kobkul Chotikanatis ◽  
Diana Weaver ◽  
Jared Ditkowsky ◽  
Yitzchok Meir Norowitz ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Chlamydia Pneumoniae ◽  
Mononuclear Cells ◽  
Tumour Necrosis Factor Alpha ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

IntroductionChlamydia pneumoniae respiratory tract infection has been implicated in the pathogenesis of reactive airway disease and asthma. Innate cytokine responses that are protective of infection with intracellular pathogens may be impaired in patients with asthma. Tumour necrosis factor alpha (TNF-α) is a cytokine related to functions of monocytes and may inhibit C. pneumoniae infection. We investigated TNF-α responses in C. pneumoniae-infected peripheral blood mononuclear cells (PBMCs) in patients with asthma and non-asthma, and whether ciprofloxacin, azithromycin or doxycycline affects TNF-α responses.MethodsPBMC (1.5×106) from paediatric patients with asthma (n=19) and non-asthmatic controls (n=6) were infected or mock infected for 1 hour with or without C. pneumoniae AR-39 at a multiplicity of infection=0.1, and cultured+ciprofloxacin, azithromycin or doxycycline (0.1 ug/mL) for 48 hours. TNF-α levels were measured in supernatants by ELISA.ResultsWhen PBMC from patients with asthma were infected with C. pneumoniae, levels of TNF-α were significantly lower than in subjects without asthma (48 hours) (5.5±5.6, 38.4±53.7; p=0.0113). However, baseline responses (no infection with C. pneumoniae) were similar in asthma and non-asthma (1.0±1.7, 1.1±1.2; p=0.89). When PBMC frompatiens with asthma were infected with C. pneumoniae+ciprofloxacin, azithromycin or doxycycline, TNF-α levels increased (25%–45%); this affect was not observed in PBMC from patients without asthma.ConclusionsWe identified differences in the quantity of TNF-α produced by C. pneumoniae-infected PBMC in asthma compared with non-asthma.

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