Effect of interleukin-1β and tumor necrosis factor-α on gene expression in human endothelial cells

2003 ◽  
Vol 284 (6) ◽  
pp. C1577-C1583 ◽  
Author(s):  
Baiteng Zhao ◽  
Salomon A. Stavchansky ◽  
Robert A. Bowden ◽  
Phillip D. Bowman
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Umbilical Vein ◽  
Interleukin 1Β ◽  
Tnf Α ◽  
Factor Α ◽  
Microarray Expression ◽  
Necrosis Factor

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.

Apolipoprotein A-I inhibits the production of interleukin-1β and tumor necrosis factor-α by blocking contact-mediated activation of monocytes by T lymphocytes

Blood ◽  
2001 ◽  
Vol 97 (8) ◽  
pp. 2381-2389 ◽  
Author(s):  
Nevila Hyka ◽  
Jean-Michel Dayer ◽  
Christine Modoux ◽  
Tadahiko Kohno ◽  
Carl K. Edwards ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
T Lymphocytes ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 1Β ◽  
Apolipoprotein A ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), essential components in the pathogenesis of immunoinflammatory diseases, are strongly induced in monocytes by direct contact with stimulated T lymphocytes. This study demonstrates that adult human serum (HS) but not fetal calf or cord blood serum displays inhibitory activity toward the contact-mediated activation of monocytes by stimulated T cells, decreasing the production of both TNF-α and IL-1β. Fractionation of HS and N-terminal microsequencing as well as electroelution of material subjected to preparative electrophoresis revealed that apolipoprotein A-I (apo A-I), a “negative” acute-phase protein, was the inhibitory factor. Functional assays and flow cytometry analyses show that high-density lipoprotein (HDL)-associated apo A-I inhibits contact-mediated activation of monocytes by binding to stimulated T cells, thus inhibiting TNF-α and IL-1β production at both protein and messenger RNA levels. Furthermore, apo A-I inhibits monocyte inflammatory functions in peripheral blood mononuclear cells activated by either specific antigens or lectins without affecting cell proliferation. These results demonstrate a new anti-inflammatory activity of HDL-associated apo A-I that might have modulating functions in nonseptic conditions. Therefore, because HDL has been shown to bind and neutralize lipopolysaccharide, HDL appears to play an important part in modulating both acute and chronic inflammation. The novel anti-inflammatory function of apo A-I reported here might lead to new therapeutic approaches in inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, and atherosclerosis.

The cytokines interleukin-1β and tumor necrosis factor-α stimulate CFTR-mediated fluid secretion by swine airway submucosal glands

2012 ◽  
Vol 303 (4) ◽  
pp. L327-L333 ◽  
Author(s):  
Nicholas Baniak ◽  
Xiaojie Luan ◽  
Amber Grunow ◽  
Terry E. Machen ◽  
Juan P. Ianowski
Keyword(s):  
Tumor Necrosis Factor ◽  
Proinflammatory Cytokines ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 1Β ◽  
Tnf Α ◽  
Submucosal Glands ◽  
Factor Α ◽  
Airway Defense ◽  
Necrosis Factor

The airway is kept sterile by an efficient innate defense mechanism. The cornerstone of airway defense is mucus containing diverse antimicrobial factors that kill or inactivate pathogens. Most of the mucus in the upper airways is secreted by airway submucosal glands. In patients with cystic fibrosis (CF), airway defense fails and the lungs are colonized by bacteria, usually Pseudomonas aeruginosa . Accumulating evidence suggests that airway submucosal glands contribute to CF pathogenesis by failing to respond appropriately to inhalation of bacteria. However, the regulation of submucosal glands by the innate immune system remains poorly understood. We studied the response of submucosal glands to the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α. These are released into the airway submucosa in response to infection with the bacterium P. aeruginosa and are elevated in CF airways. Stimulation with IL-1β and TNF-α increased submucosal gland secretion in a concentration-dependent manner with a maximal secretion rate of 240 ± 20 and 190 ± 40 pl/min, respectively. The half maximal effective concentrations were 11 and 20 ng/ml, respectively. The cytokine effect was dependent on cAMP but was independent of cGMP, nitric oxide, Ca2+, or p38 MAP kinase. Most importantly, IL-1β- and TNF-α-stimulated secretion was blocked by the CF transmembrane conductance regulator (CFTR) blocker, CFTRinh172 (100 μmol/l) but was not affected by the Ca2+-activated Cl− channel blocker, niflumic acid (1 μmol/l). The data suggest, that during bacterial infections and resulting release of proinflammatory cytokines, the glands are stimulated to secrete fluid, and this response is mediated by cAMP-activated CFTR, a process that would fail in patients with CF.

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