Modulation of Radiation – Induced Tumor Necrosis Factor α (TNF-α) Gene Expression in the Rats Spinal Cord by Melatonin

Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are two major cytokines that rise to relatively high levels during systemic inflammation, and the endothelial cell (EC) response to these cytokines may explain some of the dysfunction that occurs. To better understand the cytokine-induced responses of EC at the gene expression level, human umbilical vein EC were exposed to IL-1β or TNF-α for various times and subjected to cDNA microarray analyses to study alterations in their mRNA expression. Of ∼4,000 genes on the microarray, expression levels of 33 and 58 genes appeared to be affected by treatment with IL-1β and TNF-α, respectively; 25 of these genes responded to both treatments. These results suggest that the effects of IL-1β and TNF-α on EC are redundant and that it may be necessary to suppress both cytokines simultaneously to ameliorate the systemic response.

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Molecular cloning and characterization of mouse LITAF cDNA: role in the regulation of tumor necrosis factor-α (TNF-α) gene expression

Journal of Endotoxin Research ◽

10.1179/096805104225003780 ◽

2004 ◽

Vol 10 (1) ◽

pp. 15-23 ◽

Cited By ~ 1

Author(s):

Anne-Laure Bolcato-Bellemin ◽

Marie-Genevieve Mattei ◽

Matthew Fenton ◽

Salomon Amar

Keyword(s):

Gene Expression ◽

Tumor Necrosis Factor ◽

Molecular Cloning ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

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Lipopolysaccharide-Induced Upregulation of Tumor Necrosis Factor-α (TNF-α) in Rat Spinal Cord

Inflammation ◽

10.1007/s10753-008-9083-1 ◽

2008 ◽

Vol 31 (5) ◽

pp. 336-343 ◽

Cited By ~ 4

Author(s):

Qin Shen ◽

Dan Zhou ◽

Zhiyun Ben ◽

Chun Cheng ◽

Yonghua Liu ◽

...

Keyword(s):

Spinal Cord ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Rat Spinal Cord ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

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Insulin stimulates interleukin-6 and tumor necrosis factor-α gene expression in human subcutaneous adipose tissue

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00274.2003 ◽

2004 ◽

Vol 286 (2) ◽

pp. E234-E238 ◽

Cited By ~ 89

Author(s):

Rikke Krogh-Madsen ◽

Peter Plomgaard ◽

Pernille Keller ◽

Charlotte Keller ◽

Bente Klarlund Pedersen

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Tumor Necrosis Factor ◽

Skeletal Muscles ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

High circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are found in patients with hyperinsulinemia. Insulin stimulates release of IL-6 from adipocyte cultures, and it stimulates IL-6 gene expression in insulin-resistant, but not control, rat skeletal muscle. In addition, TNF-α may be involved in the pathogenesis of insulin resistance. Therefore, we studied the effect of insulin on IL-6 and TNF-α gene expression in human skeletal muscle and adipose tissue. Nine healthy young volunteers participated in the study. They underwent a 6-h hyperinsulinemic euglycemic clamp at a fixed insulin infusion rate, with blood glucose clamped at fasting level. Blood samples drawn at 0, 1, 2, 3, 4, 5, and 6 h were analyzed for IL-6 and TNF-α. Muscle and fat biopsies, obtained at 0, 2, 4, and 6 h, were analyzed for IL-6 and TNF-α mRNA with real-time PCR. IL-6 mRNA increased 11-, 3-, and 5-fold at 2, 4, and 6 h, respectively, in adipose tissue (ANOVA P = 0.027), whereas there was no significant effect of insulin on skeletal muscles. Plasma IL-6 increased during insulin stimulation. TNF-α mRNA increased 2.4-, 1.4-, and 2.2-fold in adipose tissue (ANOVA P = 0.001) and decreased 0.74-, 0.64-, and 0.68-fold in muscle tissue (ANOVA P = 0.04). Plasma levels of TNF-α were constant. In conclusion, the finding that insulin stimulates IL-6 and TNF-α gene expression in adipose tissue only and inhibits the TNF-α production in skeletal muscles suggests a differential regulation of muscle- and adipose tissue-derived IL-6 and TNF-α.

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The Tumor Necrosis Factor-α-blocking Agent Infliximab Inhibits Interleukin 1ß (IL-1ß) and IL-6 Gene Expression in Human Osteoblastic Cells

The Journal of Rheumatology ◽

10.3899/jrheum.081321 ◽

2009 ◽

Vol 36 (8) ◽

pp. 1575-1579 ◽

Cited By ~ 30

Author(s):

ESTELLA MUSACCHIO ◽

CHIARA VALVASON ◽

CONSTANTIN BOTSIOS ◽

FRANCESCA OSTUNI ◽

ANTONIO FURLAN ◽

...

Keyword(s):

Gene Expression ◽

Tumor Necrosis Factor ◽

Rheumatic Diseases ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Infliximab Treatment ◽

Beneficial Effects ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

Objective.Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine involved in the pathogenesis of several rheumatic diseases, including rheumatoid arthritis (RA), associated with systemic bone loss and subchondral bone erosions. TNF-α-blocking agents such as infliximab have been successful in treatment of disease-modifying antirheumatic drug-resistant rheumatic diseases. Infliximab therapy in RA also had beneficial effects on local bone destruction and bone mineral density. We assessed effects of infliximab treatment on the bone tissue compartment and cytokine profile expression in vitro.Methods.Osteoblast-like cells were exposed for 24 h to sera of RA patients collected at baseline and after 1 month (T1) and 3 years (T2) of infliximab treatment. Total RNA was extracted, and expression of interleukin 1ß (IL-1ß), IL-6, and osteoprotegerin (OPG) was measured by RT-PCR.Results.IL-1ß gene expression was significantly reduced by the T1 serum, and the same decrease was elicited by the T2 serum. IL-6 downregulation was evident with the T2 serum. OPG was unaffected.Conclusion.The finding of downregulation of inflammatory cytokines was interesting, particularly IL-6, which plays a crucial role in arthritis-related bone loss due to its involvement in osteoclast recruitment and activation. These results may represent a biological explanation and a link for the clinical observation of the beneficial effects of anti-TNF-α agents on the progression of rheumatic diseases at the bone level.

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Selected Contribution: Circadian rhythm of tumor necrosis factor-α uptake into mouse spinal cord

Journal of Applied Physiology ◽

10.1152/japplphysiol.00915.2001 ◽

2002 ◽

Vol 92 (3) ◽

pp. 1357-1362 ◽

Cited By ~ 25

Author(s):

Weihong Pan ◽

Germaine Cornélissen ◽

Franz Halberg ◽

Abba J. Kastin

Keyword(s):

Spinal Cord ◽

Circadian Rhythm ◽

Tumor Necrosis Factor ◽

Transport System ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Circadian Variation ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

Circadian variations in the actions of tumor necrosis factor-α (TNF-α) have been observed. Because a saturable transport system at the blood-brain barrier mediates most of the influx of TNF-α from blood to the central nervous system (CNS), the circadian variation of the CNS effects of TNF-α could be related to changes in this transport system. Accordingly, we measured the uptake of intravenously injected TNF-α into various CNS regions at different times and compared these measurements with the uptake into a peripheral control (muscle). We found that the spinal cord, but not the brain, showed a circadian rhythm in the uptake of TNF-α. This pattern is similar to that of leptin but different from that of interleukin-1. The circadian rhythm of the influx of TNF-α into this region of the CNS suggests a functional role for the spinal cord in the physiological actions of TNF-α.

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