scholarly journals Overexpression of Tumor Necrosis Factor-Like Ligand 1 A in Myeloid Cells Aggravates Liver Fibrosis in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Jinbo Guo ◽  
Yuxin Luo ◽  
Fengrong Yin ◽  
Xiaoxia Huo ◽  
Guochao Niu ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Liver Fibrosis ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Intestinal Inflammation ◽  
Interleukin 1 ◽  
Myeloid Cells ◽  
Biliary Cirrhosis ◽  
Necrosis Factor ◽  
Liver Tissues

Macrophages are the master regulator of the dynamic fibrogenesis–fibrosis resolution paradigm. TNF-like ligand 1 aberrance (TL1A) was found to be able to induce intestinal inflammation and fibrosis. Furthermore, significantly increased TL1A had been detected in liver tissues and mononuclear cells of patients with primary biliary cirrhosis (PBC). This study was to investigate the effect of myeloid cells with constitutive TL1A expression on liver fibrogenesis. We found that TL1A expressions in liver tissues and macrophages were significantly increased in mice with liver fibrosis induced by injection of carbon tetrachloride (CCl4). TL1A overexpression in myeloid cells induced liver function injury, accelerated the necrosis and apoptosis of hepatocytes, recruited macrophages, and promoted activation of hepatic stellate cells (HSCs) and fibrosis. In vitro results of our study showed that TL1A overexpression in macrophages promoted secretion of platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β). Culturing macrophages with TL1A overexpression could accelerate the activation and proliferation of primary HSCs. These results indicated that constitutive TL1A expression in myeloid cells exacerbated liver fibrosis, probably through macrophage recruitment and secretion of proinflammatory and profibrotic cytokines.

scholarly journals Tumor necrosis factor is the major monocyte product that increases complement receptor expression on mature human neutrophils

Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 151-158 ◽  
Author(s):  
M Berger ◽  
EM Wetzler ◽  
RS Wallis
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Time Course ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Systemic Effect ◽  
Receptor Expression ◽  
Human Neutrophils ◽  
Human Mononuclear Cells ◽  
Necrosis Factor

Interleukin-1 (IL-1) and other monocyte products have several important effects on the systemic response to infection in addition to their roles in lymphocyte stimulation. The present studies were carried out to determine whether products of stimulated monocytes activated circulating neutrophils (PMN) to increase expression of receptors for C3b (CR1) and C3bi (CR3), which are necessary for optimal margination, migration, and phagocytosis. Supernatants of human mononuclear cells that had been stimulated with lipopolysaccharide (LPS) or purified protein derivative (PPD) contained both tumor necrosis factor (TNF) and IL-1 and increased CR1 and CR3 expression on isolated PMNs. Supernatants of unstimulated cultures, media alone, or LPS or PPD alone had little or no effect. Supernatant effects were detectable at 1:3,000 final dilution and appeared to have a characteristic slow time course. These supernatants also caused dose- and time-dependent secretion of PMN granular constituents, but maximal receptor expression was accompanied by secretion of less than 10% of the cells' content of lysozyme and less than 16% of the B12 binding protein. Immunoadsorption studies showed that the supernatant's activity could be removed by anti- TNF but not by anti-IL-1. Recombinant IL-1 had no effect on receptor expression, but recombinant TNF increased CR1 and CR3 expression with kinetics similar to the supernatants. These results thus indicate that TNF is the major monocyte product that increases CR1 and CR3 expression on mature blood neutrophils. This would result in increased margination and phagocytic activity and may be an important systemic effect that would help the host eradicate infection.

Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells

Cytokine ◽  
1991 ◽  
Vol 3 (3) ◽  
pp. 189-194 ◽  
Author(s):  
Pietro Ghezzi ◽  
Charles A. Dinarello ◽  
Marina Bianchi ◽  
Mary E. Rosandich ◽  
John E. Repine ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Human Mononuclear Cells ◽  
Necrosis Factor

scholarly journals Recombinant C5a stimulates transcription rather than translation of interleukin-1 (IL-1) and tumor necrosis factor: translational signal provided by lipopolysaccharide or IL-1 itself

Blood ◽  
1990 ◽  
Vol 76 (8) ◽  
pp. 1631-1638 ◽  
Author(s):  
R Schindler ◽  
JA Gelfand ◽  
CA Dinarello
Keyword(s):  
Tumor Necrosis Factor ◽  
Transcriptional Activation ◽  
Half Life ◽  
Messenger Rna ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 1 ◽  
Cytokine Synthesis ◽  
Necrosis Factor

We investigated the effects of recombinant C5a (rC5a) on gene expression and synthesis of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) in fresh human peripheral blood mononuclear cells (PBMC). Total (cell-associated and secreted) cytokine synthesis was measured. In the strict absence of endotoxin (lipopolysaccharide [LPS]), rC5a resulted in a small but statistically insignificant increase in immunoreactive IL-1 beta and TNF, as well as in IL-1 and IL- 6 bioactivity. On the other hand, rC5a induced marked transcriptional activation of IL-1 beta and TNF in a dose-dependent fashion with an optimal concentration of 50 ng/mL. The rC5a-induced cytokine messenger RNA (mRNA) was not spontaneously translated into protein. At 50 ng/mL, rC5a induced the same levels of mRNA for IL-1 beta and TNF as 1 ng/mL of LPS, whereas LPS induced 12 times more IL-1 beta protein and 70 times more TNF protein than rC5a alone. The C5a-induced mRNA half-life was the same as that induced by LPS. Formyl-Meth-Leu-Phe (fMLP) did not induce cytokine transcription. Pretreatment with rC5a enhanced cytokine synthesis induced by other stimuli. After 2 hours of preincubation with rC5a, PBMC synthesized 3 to 10 times more IL-1 beta and TNF on subsequent stimulation by LPS or IL-1 itself. We conclude that rC5a provides primarily a transcriptional but not translational signal for IL-1 beta and TNF; the half-life of the untranslated mRNA is the same as that of translated message; rC5a-induced transcription upregulates PBMC for enhanced synthesis of these cytokines; and a translational signal can be provided by LPS or IL-1 itself.

Altered interleukin-1 and tumor necrosis factor production and secretion during pyrogenic tolerance to LPS in rabbits

1994 ◽  
Vol 267 (1) ◽  
pp. R329-R336 ◽  
Author(s):  
G. Wakabayashi ◽  
J. G. Cannon ◽  
J. A. Gelfand ◽  
B. D. Clark ◽  
K. Aiura ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Peripheral Blood Mononuclear ◽  
In Vitro Synthesis ◽  
Circulating Levels ◽  
Necrosis Factor

Rabbits were injected intravenously with 10 micrograms/kg of endotoxin [lipopolysaccharide (LPS)] on days 0, 1, and 7, and rectal temperatures were monitored. The febrile responses were compared with circulating levels of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) and in vitro synthesis of these cytokines by peripheral blood mononuclear cells (PBMC) isolated just before the injection of LPS. Fever after the first LPS injection was biphasic on day 0, attenuated and monophasic after the second LPS injection on day 1, and augmented after third injection of LPS on day 7. On day 1, circulating TNF and IL-1 beta levels were significantly (P < 0.05) decreased compared with those on days 0 and 7. Similarly, TNF and IL-1 beta synthesis by LPS-stimulated PBMC were significantly reduced on day 1. On day 7, cellular synthesis and secretion of IL-1 beta were significantly increased compared with that on day 0. A significant positive correlation was observed between fever index and total in vitro IL-1 beta synthesis by LPS-stimulated PBMC (r = 0.866, P = 0.001). These data demonstrate that pyrogenic tolerance in the rabbit after a single LPS injection is associated with decreased circulating IL-1 beta and TNF levels as well as decreased production of these cytokines in vitro. In addition, the pyrogenic hyperresponsiveness to LPS after 7 days is associated with increased synthesis and secretion of IL-1 beta from PBMC in vitro.

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