In Vitro Inhibitory Effect of Protopanaxadiol Ginsenosides on Tumor Necrosis Factor (TNF)-α Production and its Modulation by Known TNF-α Antagonists

Planta Medica ◽  
2001 ◽  
Vol 67 (3) ◽  
pp. 213-218 ◽  
Author(s):  
Jae Youl Cho ◽  
Eun Sook Yoo ◽  
Kyong Up Baik ◽  
Myung Hwan Park ◽  
Byung Hoon Han
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Inhibitory Effect ◽  
Tnf Α ◽  
Necrosis Factor

Epinephrine inhibits endotoxin-induced IL-1β production: roles of tumor necrosis factor-α and IL-10

1997 ◽  
Vol 273 (6) ◽  
pp. R1885-R1890 ◽  
Author(s):  
Tom Van Der Poll ◽  
Stephen F. Lowry
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Ex Vivo ◽  
Systemic Infection ◽  
Tnf Α ◽  
Cytokine Tumor Necrosis Factor ◽  
Dose Dependent Decrease ◽  
Factor Α ◽  
Necrosis Factor

Epinephrine has been found to inhibit the production of the proinflammatory cytokine tumor necrosis factor (TNF)-α and to enhance the production of anti-inflammatory cytokine interleukin (IL)-10. To determine the effect of epinephrine on IL-1β production, the following experiments were performed: 1) blood obtained from subjects at 4–21 h after the start of a continuous infusion of epinephrine (30 ng ⋅ kg−1⋅ min−1) produced less IL-1β after ex vivo stimulation with lipopolysaccharide (LPS), compared with blood drawn from subjects infused with saline; 2) in whole blood in vitro, epinephrine caused a dose-dependent decrease in LPS-induced IL-1β production, which was likely mediated via adrenergic receptors; and 3) inhibition of TNF and enhancement of IL-10 both contributed to epinephrine-induced inhibition of IL-1β production. Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may attenuate excessive activity of proinflammatory cytokines early in the course of systemic infection.

scholarly journals Ectopic HOXB4 overcomes the inhibitory effect of tumor necrosis factor-α on Fanconi anemia hematopoietic stem and progenitor cells

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5111-5120 ◽  
Author(s):  
Michael D. Milsom ◽  
Bernhard Schiedlmeier ◽  
Jeff Bailey ◽  
Mi-Ok Kim ◽  
Dandan Li ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Fanconi Anemia ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Ectopic Expression ◽  
Hematopoietic Stem ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

AbstractEctopic delivery of HOXB4 elicits the expansion of engrafting hematopoietic stem cells (HSCs). We hypothesized that inhibition of tumor necrosis factor-α (TNF-α) signaling may be central to the self-renewal signature of HOXB4. Because HSCs derived from Fanconi anemia (FA) knockout mice are hypersensitive to TNF-α, we studied Fancc−/− HSCs to determine the physiologic effects of HOXB4 on TNF-α sensitivity and the relationship of these effects to the engraftment defect of FA HSCs. Overexpression of HOXB4 reversed the in vitro hypersensitivity to TNF-α of Fancc−/− HSCs and progenitors (P) and partially rescued the engraftment defect of these cells. Coexpression of HOXB4 and the correcting FA-C protein resulted in full correction compared with wild-type (WT) HSCs. Ectopic expression of HOXB4 resulted in a reduction in both apoptosis and reactive oxygen species in Fancc−/− but not WT HSC/P. HOXB4 overexpression was also associated with a significant reduction in surface expression of TNF-α receptors on Fancc−/− HSC/P. Finally, enhanced engraftment was seen even when HOXB4 was expressed in a time-limited fashion during in vivo reconstitution. Thus, the HOXB4 engraftment signature may be related to its effects on TNF-α signaling, and this pathway may be a molecular target for timed pharmacologic manipulation of HSC during reconstitution.

scholarly journals Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mohammed S. AlQranei ◽  
Linda T. Senbanjo ◽  
Hanan Aljohani ◽  
Therwa Hamza ◽  
Meenakshi A. Chellaiah
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Raw 264.7 Cells ◽  
Gram Negative ◽  
Tnf Α ◽  
Necrosis Factor ◽  
In Cells

Abstract Background Lipopolysaccharide (LPS) is an endotoxin and a vital component of gram-negative bacteria’s outer membrane. During gram-negative bacterial sepsis, LPS regulates osteoclast differentiation and activity, in addition to increasing inflammation. This study aimed to investigate how LPS regulates osteoclast differentiation of RAW 264.7 cells in vitro. Results Herein, we revealed that RAW cells failed to differentiate into mature osteoclasts in vitro in the presence of LPS. However, differentiation occurred in cells primed with receptor activator of nuclear factor-kappa-Β ligand (RANKL) for 24 h and then treated with LPS for 48 h (henceforth, denoted as LPS-treated cells). In cells treated with either RANKL or LPS, an increase in membrane levels of toll-like receptor 4 (TLR4) receptor was observed. Mechanistically, an inhibitor of TLR4 (TAK-242) reduced the number of osteoclasts as well as the secretion of tumor necrosis factor (TNF)-α in LPS-treated cells. RANKL-induced RAW cells secreted a very basal level TNF-α. TAK-242 did not affect RANKL-induced osteoclastogenesis. Increased osteoclast differentiation in LPS-treated osteoclasts was not associated with the RANKL/RANK/OPG axis but connected with the LPS/TLR4/TNF-α tumor necrosis factor receptor (TNFR)-2 axis. We postulate that this is because TAK-242 and a TNF-α antibody suppress osteoclast differentiation. Furthermore, an antibody against TNF-α reduced membrane levels of TNFR-2. Secreted TNF-α appears to function as an autocrine/ paracrine factor in the induction of osteoclastogenesis independent of RANKL. Conclusion TNF-α secreted via LPS/TLR4 signaling regulates osteoclastogenesis in macrophages primed with RANKL and then treated with LPS. Our findings suggest that TLR4/TNF-α might be a potential target to suppress bone loss associated with inflammatory bone diseases, including periodontitis, rheumatoid arthritis, and osteoporosis.

scholarly journals Lipoxin (LX)A4 and Aspirin-triggered 15-epi-LXA4 Inhibit Tumor Necrosis Factor 1α–initiated Neutrophil Responses and Trafficking: Regulators of a Cytokine–Chemokine Axis

1999 ◽  
Vol 189 (12) ◽  
pp. 1923-1930 ◽  
Author(s):  
Mohamed Hachicha ◽  
Marc Pouliot ◽  
Nicos A. Petasis ◽  
Charles N. Serhan
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Gm Csf ◽  
Tnf Α ◽  
Human Polymorphonuclear Leukocytes ◽  
The Impact ◽  
Receptor Antibodies ◽  
Necrosis Factor

The impact of  lipoxin A4 (LXA4) and aspirin-triggered lipoxins (ATLs) was investigated in tumor necrosis factor (TNF)-α–initiated neutrophil (polymorphonuclear leukocyte) responses in vitro and in vivo using metabolically stable LX analogues. At concentrations as low as 1–10 nM, the LXA4 and ATL analogues each inhibited TNF-α–stimulated superoxide anion generation and IL-1β release by human polymorphonuclear leukocytes. These LXA4-ATL actions were time and concentration dependent and proved selective for TNF-α, as these responses were not altered with either GM-CSF– or zymosan-stimulated cells. TNF-α–induced IL-1β gene expression was also regulated by both anti-LXA4 receptor antibodies and LXA4-ATL analogues. In murine air pouches, 15R/S-methyl-LXA4 dramatically inhibited TNF-α–stimulated leukocyte trafficking, as well as the appearance of both macrophage inflammatory peptide 2 and IL-1β, while concomitantly stimulating IL-4 in pouch exudates. Together, these results indicate that both LXA4 and ATL regulate TNF-α–directed neutrophil actions in vitro and in vivo and stimulate IL-4 in exudates, playing a pivotal role in immune responses.

Inhibitory effect of nicotinamide on in vitro and in vivo production of tumor necrosis factor-α

1997 ◽  
Vol 59 (1) ◽  
pp. 7-11 ◽  
Author(s):  
Masamitsu Fukuzawa ◽  
Jo Satoh ◽  
Gen Muto ◽  
Yoshiko Muto ◽  
Sachiko Nishimura ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Inhibitory Effect ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Dexamethasone Restores the Repressive Effect of Tumor Necrosis Factor-α on Follicular Growth and E2 Secretion During the In Vitro Culture of Preantral Follicles

2021 ◽  
Author(s):  
Que Wu ◽  
Tingwei Zhuang ◽  
Zhiling Li
Keyword(s):  
Tumor Necrosis Factor ◽  
In Vitro Culture ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Follicular Growth ◽  
Tnf Α ◽  
Repressive Effect ◽  
Factor Α ◽  
Necrosis Factor

AbstractAs a proinflammatory cytokine, tumor necrosis factor-α (TNF-α) is central to the female reproductive tract and affects various phases of follicular development and uterine cycles. High levels of TNF-α play a vital role in the pathogenesis of polycystic ovary syndrome (PCOS) in patients. Clinicians know that dexamethasone can inhibit the induction of androgen by suppressing the adrenal glands which improves the status of the endocrine system in PCOS patients. We hypothesize that dexamethasone has much more functionality and can exert a therapeutic effect by antagonizing TNF-α. We added TNF-α to the follicular culture medium to simulate the high TNF-α levels observed in the endocrine environment of PCOS patients. Dexamethasone was added to the medium to determine if it could counteract the inhibitory effect of TNF-α on follicular growth and 17β-estradiol (E2) secretion. Follicular diameter, E2 concentration, follicle survival, antral-like cavity formation, and ovulation were measured to assess the effects of dexamethasone. In our work, TNF-α inhibited in vitro follicular growth and E2 secretion in a dose-dependent manner. Based on the results of the present research, we concluded that the addition of dexamethasone partially counteracts the repressive effect of TNF-α on follicle growth and E2 secretion during in vitro culture of the preantral follicles of mice. Thus, the findings in this paper suggest that dexamethasone may act as a therapy by counteracting the effects of TNF-α in PCOS patients. These results provide a new foundation for exploring the treatment of PCOS patients with dexamethasone.

scholarly journals Tumor Necrosis Factor-Alpha Exacerbates Viral Entry in SARS-CoV2-Infected iPSC-Derived Cardiomyocytes

2021 ◽  
Vol 22 (18) ◽  
pp. 9869
Author(s):  
Chiu-Yang Lee ◽  
Chih-Heng Huang ◽  
Elham Rastegari ◽  
Vimalan Rengganaten ◽  
Ping-Cheng Liu ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Viral Entry ◽  
Tumor Necrosis ◽  
Myocardial Damage ◽  
Host Cells ◽  
Necrosis Factor Alpha ◽  
Successful Infection ◽  
Tnf Α ◽  
Necrosis Factor

The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.

scholarly journals Tumor necrosis factor alpha reduces intestinal vitamin C uptake: a role for NF-κB-mediated signaling

2018 ◽  
Vol 315 (2) ◽  
pp. G241-G248 ◽  
Author(s):  
Veedamali S. Subramanian ◽  
Subrata Sabui ◽  
Ganapathy A. Subramenium ◽  
Jonathan S. Marchant ◽  
Hamid M. Said
Keyword(s):  
Tumor Necrosis Factor ◽  
Vitamin C ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Tnf Α ◽  
Sodium Dependent ◽  
Factor Α ◽  
Necrosis Factor

Sodium-dependent vitamin C transporter-1 (SVCT-1) is the major transporter mediating intestinal vitamin C uptake. Intestinal inflammation and prolonged infection are associated with increased serum and intestinal mucosa levels of tumor necrosis factor-α (TNF-α), which also exerts profound effects on the intestinal absorption process. Elevated levels of TNF-α have been linked to the pathogenesis of inflammatory bowel disease (IBD) and malabsorption of nutrients, and patients with this condition have low levels of vitamin C. To date, little is known about the effect of TNF-α on intestinal absorption of vitamin C. We studied the impact of TNF-α on ascorbic acid (AA) transport using a variety of intestinal preparations. The expression level of human SVCT-1 mRNA is significantly lower in patients with IBD. TNF-α treated Caco-2 cells and mice showed a significant inhibition of intestinal14C-AA uptake. This inhibition was associated with significant decreases in SVCT-1 protein, mRNA, and heterogeneous nuclear RNA levels in TNF-α treated Caco-2 cells, mouse jejunum, and enteroids. Also, TNF-α caused a significant inhibition in the SLC23A1 promoter activity. Furthermore, treatment of Caco-2 cells with celastrol (NF-κB inhibitor) blocked the inhibitory effect caused by TNF-α on AA uptake, SVCT-1 protein, and mRNA expression, as well as the activity of SLC23A1 promoter. Treatment of TNF-α also led to a significant decrease in the expression of hepatocyte nuclear factor-1-α, which drives the basal activity of SLC23A1 promoter, and this effect was reversed by celastrol. Together, these findings show that TNF-α inhibits intestinal AA uptake, and this effect is mediated, at least in part, at the level of transcription of the SLC23A1 gene via the NF-κB pathway.NEW & NOTEWORTHY Our findings show that tumor necrosis factor-α inhibits intestinal ascorbic acid uptake in both in vitro and in vivo systems, and this inhibitory effect is mediated, at least in part, at the level of transcription of the SLC23A1 (sodium-dependent vitamin C transporter-1) gene via the NF-κB pathway.

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