Tumor Necrosis Factor-alpha Group Research Articles

Mechanism of Receptor-Interacting Protein 3 on Tumor Necrosis Factor Alpha in Gallbladder Cancer Cells

To investigate the mechanism of receptor-interacting protein 3 on the proliferation, invasion and reactive oxygen species levels of gallbladder cancer cells induced by tumor necrosis factor alpha. Gallbladder cancer SGC-996 cells were divided into a control group, a plasmid cloning deoxyribonucleic acid-negative control group, a plasmid cloning deoxyribonucleic acid-receptor-interacting protein 3 group, a plasmid cloning deoxyribonucleic acid-receptor-interacting protein 3+tumor necrosis factor alpha group and a plasmid cloning deoxyribonucleic acid-receptor-interacting protein 3+si-receptor-interacting protein 3 group. Reverse transcription polymerase chain reaction for messenger ribonucleic acid expression in cells; detection of cell proliferation, invasion and reactive oxygen species in cells by cell counting kit-8, Transwell and flow cytometry, respectively; detection of receptor-interacting protein 3, matrix metallopeptidase-9, matrix metallopeptidase-2 proteins in cells (Western blotting method). The expression of receptor-interacting protein 3 messenger ribonucleic acid was lower in gallbladder cancer cells than in gallbladder epithelial cells (p<0.05) and lowest in SGC-996 cells (p<0.05). receptor-interacting protein 3 messenger ribonucleic acid, cell survival rate, invasion ability, reactive oxygen species level, receptorinteracting protein 3, matrix metallopeptidase-2 and matrix metallopeptidase-9 protein were similar in the control and plasmid cloning deoxyribonucleic acid-negative control groups (p>0.05), while receptorinteracting protein 3 messenger ribonucleic acid, receptor-interacting protein 3 protein, reactive oxygen species content were elevated. And cell survival, invasion ability, matrix metallopeptidase-2 and matrix metallopeptidase-9 protein were decreased in the plasmid cloning deoxyribonucleic acid-receptorinteracting protein 3 group (p<0.05). Compared with the plasmid cloning deoxyribonucleic acid-receptorinteracting protein 3 group, receptor-interacting protein 3 protein, reactive oxygen species content were increased and cell survival, invasion ability, matrix metallopeptidase-2 and matrix metallopeptidase-9 protein were decreased in the plasmid cloning deoxyribonucleic acid-receptor-interacting protein 3+tumor necrosis factor alpha group and receptor-interacting protein 3 protein, reactive oxygen species content were decreased and cell survival, invasion ability, matrix metallopeptidase-2 and matrix metallopeptidase-9 protein were increased in the plasmid cloning deoxyribonucleic acid-receptor-interacting protein 3+sireceptor interacting protein 3 group (p<0.05). Overexpression of receptor-interacting protein 3 inhibited tumor necrosis factor alpha induced proliferation and invasion of gallbladder cancer cells and promoted reactive oxygen species levels in tumor necrosis factor alpha induced gallbladder cancer cells and its mechanism was related to matrix metallopeptidase-2 and matrix metallopeptidase-9 protein expression.

The levels of neuropeptide S in the brain of asthmatic mice with anxiety and the relationship with the inflammatory mediators

Objective: To investigate the levels of neuropeptide S in the brain of asthmatic mice with anxiety and the effects of inflammatory mediatores on changes of neuropeptide S in in vitro experiments. Methods: According to the random number table method, 40 BALB/C mice were randomly divided into 4 groups: the control group, the asthma group, the anxiety group and the asthma and anxiety group. The relative expressions of neuropeptide S mRNA in the brain tissue of each group were detected by quantitative real-time polymerase chain reaction(QRT-PCR). Rat cortex neurons obtained by primary culture were divided into 4 groups: the PBS control group, the interleukin-1 beta group, the interleukin-6 group and the tumor necrosis factor-alpha group. After stimulation with inflammatory cytokines the mRNA expressions of neuropeptide S were measured by QRT-PCR and neuropeptide S levels in the cell culture supernatants were measured by emzyme linked immunosorbent assay(ELISA). Results: The relative expressions of neuropeptide S mRNA were decreased in the anxiety group(0.87±0.05) and the asthma and anxiety group(0.79±0.03)compared with the control group(1.00±0.05)and the asthma group(0.96±0.06), most notably in the asthma and anxiety group (all P<0.05). Compared to the PBS control group[(1.00±0.06), (50.6±1. 8)ng/L] and the interleukin-1 beta group[(0.94±0.08), (49.5±1.0)ng/L], the levels of neuropeptide S mRNA and neuropeptide S were decreased in the interleukin-6 group[(0.88±0.07), (45.4±1.2)ng/L] and the tumor necrosis factor-alpha group[(0.86±0.07), (46.0±1.0)ng/L](all P<0.05). There were no significant differences between the interleukin-1 beta group and the PBS control group(all P>0.05). Conclusions: Up-regulated interleukin-6 and tumor necrosis factor-alpha in asthma can inhibit the secretion of neuropeptide S in neuronal cells. The decline of brain neuropeptide S, which has anti-anxiety effect, may lead to the occurrence of anxiety, which may be a potential mechanism of comorbidity of asthma and anxiety.

Correction: Therapeutic Non-Toxic Doses of TNF Induce Significant Regression in TNFR2-p75 Knockdown Lewis Lung Carcinoma Tumor Implants

Tumor necrosis factor-alpha (TNF) binds to two receptors: TNFR1/p55-cytotoxic and TNFR2/p75-pro-survival. We have shown that tumor growth in p75 knockout (KO) mice was decreased more than 2-fold in Lewis lung carcinoma (LLCs). We hypothesized that selective blocking of TNFR2/p75 LLCs may sensitize them to TNF-induced apoptosis and affect the tumor growth. We implanted intact and p75 knockdown (KD)-LLCs (>90%, using shRNA) into wild type (WT) mice flanks. On day 8 post-inoculation, recombinant murine (rm) TNF-α (12.5 ng/gr of body weight) or saline was injected twice daily for 6 days. Tumor volumes (tV) were measured daily and tumor weights (tW) on day 15, when study was terminated due to large tumors in LLC+TNF group. Tubular bones, spleens and peripheral blood (PB) were examined to determine possible TNF toxicity. There was no significant difference in tV or tW between LLC minus (-) TNF and p75KD/LLC-TNF tumors. Compared to 3 control groups, p75KD/LLC+TNF showed >2-5-fold decreases in tV (p<0.001) and tW (p<0.0001). There was no difference in tV or tW end of study vs. before injections in p75KD/LLC+TNF group. In 3 other groups tV and tW were increased 2.7-4.5-fold (p<0.01, p<0.0002 and p<0.0001). Pathological examination revealed that 1/3 of p75KD/LLC+rmTNF tumors were 100% necrotic, the remaining revealed 40-60% necrosis. No toxicity was detected in bone marrow, spleen and peripheral blood. We concluded that blocking TNFR2/p75 in LLCs combined with intra-tumoral rmTNF injections inhibit LLC tumor growth. This could represent a novel and effective therapy against lung neoplasms and a new paradigm in cancer therapeutics.

Therapeutic Non-Toxic Doses of TNF Induce Significant Regression in TNFR2-p75 Knockdown Lewis Lung Carcinoma Tumor Implants

Tumor necrosis factor-alpha (TNF) binds to two receptors: TNFR1/p55-cytotoxic and TNFR2/p75-pro-survival. We have shown that tumor growth in p75 knockout (KO) mice was decreased more than 2-fold in Lewis lung carcinoma (LLCs). We hypothesized that selective blocking of TNFR2/p75 LLCs may sensitize them to TNF-induced apoptosis and affect the tumor growth. We implanted intact and p75 knockdown (KD)-LLCs (>90%, using shRNA) into wild type (WT) mice flanks. On day 8 post-inoculation, recombinant murine (rm) TNF-α (12.5 ng/gr of body weight) or saline was injected twice daily for 6 days. Tumor volumes (tV) were measured daily and tumor weights (tW) on day 15, when study was terminated due to large tumors in LLC+TNF group. Tubular bones, spleens and peripheral blood (PB) were examined to determine possible TNF toxicity. There was no significant difference in tV or tW between LLC minus (-) TNF and p75KD/LLC-TNF tumors. Compared to 3 control groups, p75KD/LLC+TNF showed >2-5-fold decreases in tV (p<0.001) and tW (p<0.0001). There was no difference in tV or tW end of study vs. before injections in p75KD/LLC+TNF group. In 3 other groups tV and tW were increased 2.7-4.5-fold (p<0.01, p<0.0002 and p<0.0001). Pathological examination revealed that 1/3 of p75KD/LLC+rmTNF tumors were 100% necrotic, the remaining revealed 40-60% necrosis. No toxicity was detected in bone marrow, spleen and peripheral blood. We concluded that blocking TNFR2/p75 in LLCs combined with intra-tumoral rmTNF injections inhibit LLC tumor growth. This could represent a novel and effective therapy against lung neoplasms and a new paradigm in cancer therapeutics.

Cardiopulmonary effects of tumor necrosis factor-alpha in the piglet: influence of cyclooxygenase inhibition.

Tumor necrosis factor-alpha (TNF) is believed to play an important role in mediating many of the pathophysiologic changes accompanying bacterial sepsis. In order to characterize the cardiopulmonary responses to TNF in a young animal model and to determine to what extent these changes were secondary to cyclooxygenase byproducts, three groups of mechanically ventilated piglets received an infusion of either TNF, indomethacin followed by TNF (Indo+TNF) or neither (control). Compared to controls at 120 min, TNF resulted in the following changes beginning 30-60 min after the infusion began: mean pulmonary artery pressure (Ppa) increased from 1.7 +/- 0.3 to 4.4 +/- 0.7 kPa (13 +/- 2 to 33 +/- 5 mm Hg) (p < 0.001); cardiac output (CO) fell from 0.28 +/- 0.05 to 0.20 +/- 0.07 liters/kg/min (p < 0.01); mean arterial blood pressure (Psa) decreased from 9.5 +/- 1.2 to 7.9 +/- 1.9 kPa (71 +/- 9 to 59 +/- 14 mm Hg) as did pH from 7.49 +/- 0.04 to 7.13 +/- 0.17 (p < 0.001). Dynamic lung compliance (Cdyn) also decreased; however, pulmonary resistance (RI) remained unchanged. Thromboxane B2 (TxB2) rose in all animals at 60 min coincident with Psa elevation and was significantly blocked by Indo (p < 0.03). In the Indo+TNF group the early TNF-induced rise in Psa was blunted compared to the TNF group [2.9 +/- 1.2 vs. 3.6 +/- 0.8 kPa (22 +/- 3 vs. 27 +/- 6 mm Hg; p < 0.04)] as were the late decreases in pH and Psa (p < 0.04). There were no significant changes in Cdyn secondary to Indo. Although delayed, the hemodynamic changes observed with TNF infusion are similar to those reported for piglets receiving group B streptococci; however, in contrast to the latter the early changes secondary to TNF are only mildly effected by indomethacin. The significant improvement in the late occurring hypotension and acidosis suggests that TNF may act in part via the cyclooxygenase pathway as a mediator of the late hypotension associated with sepsis.

Pentoxifylline Prevents Tumor Necrosis Factor-induced Lung Injury

Human tumor necrosis factor-alpha (TNF) is a monokine produced by mononuclear cells after many stimuli, including bacterial endotoxin. Full exploration of its antineoplastic effects has been limited by side effects. We have previously shown that the administration of TNF to guinea pigs is associated with a syndrome similar to gram-negative septic shock, which includes capillary permeability lung injury. In this study, we measured the effects of pentoxifylline (PTX) on parameters of TNF-induced lung injury including: lung wet-to-dry weight ratio, the ratio of lung-to-plasma 125I-labeled albumin (albumin index), bronchoalveolar lavage (BAL) and peripheral leukocyte counts, and serial measurements of mean arterial pressure (MAP). Four groups of animals were studied: a TNF group received 3.75 x 10(6) U/kg TNF; a PTX group received a 20-mg/kg bolus of PTX followed by an infusion of 6 mg/kg/h; the PTX-TNF group received both; and the final group was a saline control. ANOVA analysis revealed significant elevations of lung wet-to-dry ratio only in the TNF group (5.9 [5.6 to 6.3], p less than 0.001), expressed as the mean followed by 95% confidence intervals). Lung albumin index was elevated only in the TNF group (0.24 [0.19 to 0.29], p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)