Oxyresveratrol dampens neuroimmune responses in vivo: a selective effect on TNF-α

Consumption of nutrients rich in hydroxystilbenes has been promoted because of their health benefits, including dampening of inflammatory responses. However, few studies have examined their effects in vivo. Here, we show that the hydroxystilbene oxyresveratrol (trans-2,3′,4,5′-tetrahydroxystilbene: o-RES) blocked hypothermia but caused no significant effect on the febrile response to the immune stimulus, bacterial LPS in rats. This was associated with a reduction in the LPS-induced plasma cytokine, tumor necrosis factor (TNF)-α, but not IL-6. Both IL-6-stimulated STAT-3 and LPS-induced cycoloxygenase-2 expression in the hypothalamus were not affected by o-RES. These data strongly suggest that the o-RES-induced dampening of neuroimmune responses is largely due to its inhibitory effect on TNF-α production. In contrast to in vitro experiments, o-RES has no direct effect on NF-κB signaling pathway in vivo. The specific inhibitory effect of o-RES on TNF-α opens new avenues for the clinical use of o-RES in pathological conditions where excessive production of TNF-α is deleterious.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.6.r1885 ◽

1997 ◽

Vol 273 (6) ◽

pp. R1885-R1890 ◽

Cited By ~ 3

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.

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Neutrophil recruitment inhibitory factor: a possible candidate for a novel cytokine

Mediators of Inflammation ◽

10.1155/s0962935192000103 ◽

1992 ◽

Vol 1 (1) ◽

pp. 49-54 ◽

Cited By ~ 1

Author(s):

W. M. S. C. Tamashiro ◽

B. M. Tavares-Murta ◽

F. Q. Cunha ◽

M. C. Roque-Barreira ◽

R. M. D. Nogueira ◽

...

Keyword(s):

Inhibitory Activity ◽

Inflammatory Responses ◽

Neutrophil Migration ◽

Gel Filtration ◽

Inhibitory Effect ◽

Neutrophil Recruitment ◽

Tnf Α ◽

Inflammatory Stimuli

Inhibitory effect upon neutrophil migration to the inflammatory focus was previously detected in the cell-free incubation fluid of lipopolysaccharide (LPS)-stimulated macrophage monolayers. In the present study we showed that the neutrophil recruitment inhibitory activity from this supernatant was mainly detected in a fraction (P2) obtained by gel filtration chromatography on Sephacryl S-300. P2 fraction was able to inhibit ‘in vivo’ neutrophil emigration induced by different inflammatory stimuli, but it did not affect ‘in vitro’ neutrophil chemotaxis induced by FMLP. When injected intravenously, P2 inhibited oedema induced by carrageenin or immunological stimulus but not the oedema induced by dextran, thus affecting cell-dependent inflammatory responses. It was observed that P2 also induced neutrophil migration when injected locally in peritoneal cavities. This activity was significantly reduced by pretreatment of the animals with dexamethasone. Cytokines, such as IL-8 and TNF-α that are known to exhibit inhibitory effect upon neutrophil migration, were not detected in P2 fraction by highly sensitive assays. Overall the results suggest the existence of a novel cytokine exhibiting ‘in vivo’ neutrophil inhibitory activity, referred as NRIF.

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

Planta Medica ◽

10.1055/s-2001-12005 ◽

2001 ◽

Vol 67 (3) ◽

pp. 213-218 ◽

Cited By ~ 57

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

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Tumor Necrosis Factor-α (TNF-α) Stimulates Chemotactic Response in Mouse Myogenic Cells

Cell Transplantation ◽

10.3727/000000003783985115 ◽

2003 ◽

Vol 12 (1) ◽

pp. 91-100 ◽

Cited By ~ 54

Author(s):

Y. Torrente ◽

E. El Fahime ◽

N. J. Caron ◽

R. Del Bo ◽

M. Belicchi ◽

...

Keyword(s):

Muscle Injury ◽

Tumor Necrosis ◽

Chemotactic Activity ◽

Myogenic Cells ◽

Tnf Α ◽

Myoblast Transplantation ◽

Factor Α ◽

Necrosis Factor

Migration of transplanted myogenic cells occurs during both embryogenesis and regeneration of skeletal muscles and is important for successful myoblast transplantation, but little is known about factors that promote chemotaxis of these cells. Tumor necrosis factor-α (TNF-α) is known to induce chemotactic effect on several cell types. In this study, we investigated its influence on the in vitro and in vivo motility of C2C12 and primary myoblasts. In the in vitro test performed in the blind-well Boyden chambers, we showed that TNF-α (50–400 U/ml) significantly enhanced the ability of myogenic cells to migrate. The dose–response curve for this factor was bell shaped, with maximum activity in the 200 U/ml range. In the in vivo test, intramuscular administration of TNF-α was performed by an Alzet pump connected to a perforated polyethylene microtube inserted in the tibialis anterior (TA) of CD1 mice. In these experiments, myoblasts were injected under the muscle epimysium. The recipient mice were immunosuppressed with FK506. Our results showed that, 5 days after myoblast transplantation, cells migrated further in the muscles infused with TNF-α than in the muscles not exposed to TNF-α. TNF-α not only has a chemotactic activity but may also modify cell migration via its action on matrix metalloproteinase (MMP) expression. The proteolytic activities of the MMPs secreted in the muscles were thus also assessed by gelatin zymography. The results showed an increased of MMP-2 and MMP-9 transcripts in the TNF-α-infused muscles injected with myogenic cells. Myoblast migration during transplantation may be enhanced by overlapping gradients of several effector molecules such as TNF-α, interferon-γ (INF-γ), and interleukins, released at the site of muscle injury. We propose that TNF-α may promote myoblast migration directly through chemotactic activity and indirectly by enhancing MMP activity at the site of muscle injury.

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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

Journal of Experimental Medicine ◽

10.1084/jem.189.12.1923 ◽

1999 ◽

Vol 189 (12) ◽

pp. 1923-1930 ◽

Cited By ~ 143

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.

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

Immunology Letters ◽

10.1016/s0165-2478(97)00088-6 ◽

1997 ◽

Vol 59 (1) ◽

pp. 7-11 ◽

Cited By ~ 24

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

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Differential Tumor Necrosis Factor Alpha Expression and Release from Peritoneal Mouse Macrophages In Vitro in Response to Proliferating Gram-Positive versus Gram-Negative Bacteria

Infection and Immunity ◽

10.1128/iai.68.8.4422-4429.2000 ◽

2000 ◽

Vol 68 (8) ◽

pp. 4422-4429 ◽

Cited By ~ 18

Author(s):

Wei Cui ◽

David C. Morrison ◽

Richard Silverstein

Keyword(s):

Tumor Necrosis ◽

Necrosis Factor Alpha ◽

Gram Negative ◽

E Coli ◽

Tnf Α ◽

Mouse Macrophages ◽

Factor Alpha ◽

Necrosis Factor

ABSTRACT Viable Escherichia coli and Staphylococcus aureus bacteria elicited markedly different in vitro tumor necrosis factor alpha (TNF-α) responses when placed in coculture with peritoneal murine macrophages. These include quantitative differences in TNF-α mRNA expression and corresponding protein product secretion as well as kinetic differences in the profiles of the TNF-α responses. Further, lipopolysaccharide (from E. coli) is a major contributing factor to these differences, as revealed by comparative experiments with endotoxin-responsive (C3Heb/FeJ) and endotoxin-hyporesponsive (C3H/HeJ) macrophages. Nevertheless, the eventual overall magnitude of the TNF-α secretion of macrophages in response to S. aureus was at least equivalent to that observed with E. coli, while appearing at time periods hours later than the E. coli-elicited TNF-α response. Both the magnitude and kinetic profile of the TNF-α responses were found to be relatively independent of the rate of bacterial proliferation, at least to the extent that similar results were observed with both viable and paraformaldehyde-killed microbes. Nevertheless, S. aureus treated in culture with the carbapenem antibiotic imipenem manifests markedly altered profiles of TNF-α response, with the appearance of an early TNF-α peak not seen with viable organisms, a finding strikingly similar to that recently reported by our laboratory from in vivo studies (R. Silverstein, J. G. Wood, Q. Xue, M. Norimatsu, D. L. Horn, and D. C. Morrison, Infect. Immun. 68:2301–2308, 2000). In contrast, imipenem treatment of E. coli-cocultured macrophages does not significantly alter the observed TNF-α response either in vitro or in vivo. In conclusion, our data support the concept that the host inflammatory response of cultured mouse macrophages in response to viable gram-positive versus gram-negative microbes exhibits distinctive characteristics and that these distinctions are, under some conditions, altered on subsequent bacterial killing, depending on the mode of killing. Of potential importance, these distinctive in vitro TNF-α profiles faithfully reflect circulating levels of TNF-α in infected mice. These results suggest that coculture of peritoneal macrophages with viable versus antibiotic-killed bacteria and subsequent assessment of cytokine response (TNF-α) may be of value in clarifying, and ultimately controlling, related host inflammatory responses in septic patients.

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Comparison of In Vitro and In Vivo Antioxidant Activities of Six Flavonoids with Similar Structures

Antioxidants ◽

10.3390/antiox9080732 ◽

2020 ◽

Vol 9 (8) ◽

pp. 732

Author(s):

Yixiu Zeng ◽

Jiajia Song ◽

Meimei Zhang ◽

Hongwei Wang ◽

Yu Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Sulfonic Acid ◽

Tumor Necrosis ◽

Antioxidant Activities ◽

Antioxidative Capacity ◽

Tnf Α ◽

Total Antioxidative Capacity ◽

Necrosis Factor

The in vitro and in vivo antioxidant activities of six flavonoids with similar structures, including epicatechin (EC), epigallocatechin (EGC), procyanidin B2 (P), quercetin (Q), taxifolin (T), and rutin (R) were compared. The structures of the six flavonoids and their scavenging activities for 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radicals were closely related. The flavonoids decreased serum contents of malondialdehyde (MDA) and nitric oxide (NO), and increased serum total antioxidative capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels to different degrees in d-galactose-treated mice. The changes in mRNA expression of liver GSH-Px1, CAT, SOD1, and SOD2 by d-galactose were dissimilarly restored by the six flavonoids. Moreover, the six flavonoids differentially prevented the inflammatory response caused by oxidative stress by inhibiting interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels, and restoring IL-10 levels. These six flavonoids from two subclasses revealed the following antioxidant capability: P > EC, EGC > EC, Q > T, Q > R. Our results indicate that (1) the pyrogallol, dimerization, and C2=C3 double bonds of flavonoids enhanced antioxidant activity and (2) the C3 glycosylation of flavonoids attenuated antioxidant capacity.

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