scholarly journals Secretion imbalance between tumour necrosis factor and its inhibitor in inflammatory bowel disease

Gut ◽  
1998 ◽  
Vol 43 (2) ◽  
pp. 203-209 ◽  
Author(s):  
M Noguchi ◽  
N Hiwatashi ◽  
Z Liu ◽  
T Toyota
Keyword(s):  
Lamina Propria ◽  
Mononuclear Cells ◽  
Tnf Receptor ◽  
Tnf Receptors ◽  
Lamina Propria Mononuclear Cells ◽  
Tnf Α ◽  
Soluble Tnf Receptors ◽  
Inflammatory Bowel ◽  
Soluble Tnf Receptor ◽  
Necrosis Factor

Background—Tumour necrosis factor (TNF) α and TNF-β are soluble ligands binding to TNF receptors with similar activities; soluble TNF receptors neutralise TNF activity by acting as inhibitors. Little is known about the cytokine/soluble receptor role in inflammatory bowel disease (IBD).Aims—To test the hypothesis that an imbalance in secretion between TNF and TNF inhibitors plays a role in gut inflammation in patients with IBD.Methods—The secretion of TNF-α, TNF-β, and soluble TNF receptors was compared in the culture supernatants of colonic biopsy specimens and isolated lamina propria mononuclear cells from patients with active colonic IBD.Results—Spontaneous secretion of TNF-α in involved IBD mucosa was higher than in normal control and self limited colitis mucosa. Secretion of TNF-β was higher in patients with Crohn’s disease than in those with ulcerative colitis. Soluble TNF receptor in IBD mucosa inhibited TNF activity. Type 2 soluble receptor release from IBD mucosa was increased in active inflammation; release from lamina propria cells was not increased. Mucosal TNF-α production correlated with severity of disease.Conclusions—Results showed enhanced secretion of TNF-α but failure to release enhanced amounts of soluble TNF receptor in lamina propria mononuclear cells of patients with IBD. An imbalance in secretion between TNF and TNF inhibitor may be implicated in the pathogenesis of IBD.

Tu1922 Genome-Wide Epigenomic Analysis of Lamina Propria Mononuclear Cells of Inflammatory Bowel Disease

2012 ◽  
Vol 142 (5) ◽  
pp. S-878-S-879
Author(s):  
Takeshi Otsubo ◽  
Yuki I. Kawamura ◽  
Kenshiro Oshima ◽  
Takaho A. Endo ◽  
Tetsuro Toyoda ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Lamina Propria ◽  
Bowel Disease ◽  
Mononuclear Cells ◽  
Lamina Propria Mononuclear Cells ◽  
Genome Wide ◽  
Inflammatory Bowel

LPS induces apoptosis in macrophages mostly through the autocrine production of TNF-α

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3823-3831 ◽  
Author(s):  
Jordi Xaus ◽  
Mònica Comalada ◽  
Annabel F. Valledor ◽  
Jorge Lloberas ◽  
Francisco López-Soriano ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Endotoxic Shock ◽  
Late Phase ◽  
No Synthase ◽  
Tnf Receptor ◽  
Tnf Receptors ◽  
Tnf Α ◽  
Early Apoptosis ◽  
Induced Apoptosis ◽  
Necrosis Factor

The deleterious effects of lipopolysaccharide (LPS) during endotoxic shock are associated with the secretion of tumor necrosis factor (TNF) and the production of nitric oxide (NO), both predominantly released by tissue macrophages. We analyzed the mechanism by which LPS induces apoptosis in bone marrow-derived macrophages (BMDM). LPS-induced apoptosis reached a plateau at about 6 hours of stimulation, whereas the production of NO by the inducible NO-synthase (iNOS) required between 12 and 24 hours. Furthermore, LPS-induced early apoptosis was only moderately reduced in the presence of an inhibitor of iNOS or when using macrophages from iNOS -/-mice. In contrast, early apoptosis was paralleled by the rapid secretion of TNF and was almost absent in macrophages from mice deficient for one (p55) or both (p55 and p75) TNF-receptors. During the late phase of apoptosis (12-24 hours) NO significantly contributed to the death of macrophages even in the absence of TNF-receptor signaling. NO-mediated cell death, but not apoptosis induced by TNF, correlated with the induction of p53 and Bax genes. Thus, LPS-induced apoptosis results from 2 independent mechanisms: first and predominantly, through the autocrine secretion of TNF- (early apoptotic events), and second, through the production of NO (late phase of apoptosis).

scholarly journals Burn injury induces intestinal inflammatory response mediated by Th17 in burn-primed endotoxemic mice

2020 ◽  
Author(s):  
Kazuhiko Sekine ◽  
Takayuki Shibusawa ◽  
Seitaro Fujishima ◽  
Naoki Aikawa ◽  
Junichi Sasaki
Keyword(s):  
Lamina Propria ◽  
Mononuclear Cells ◽  
Burn Injury ◽  
Inflammatory Responses ◽  
Total Body Surface Area ◽  
Vital Role ◽  
Mice Model ◽  
Th17 Response ◽  
Lamina Propria Mononuclear Cells ◽  
Tnf Α

Objective: This study aimed to elucidate the mechanism underlying the susceptibility to infection-related acute lung injury by focusing on the role of gut mucosal T-helper (Th) 17 cells that preferentially produce IL-17 with probiotics in a burn-primed endotoxemic mice model. Methods: Mice were subjected to a 15% total body surface area third-degree burn. Survival from lethal lipopolysaccharide (LPS) administration (3 mg/kg) on 11th day post burn was assessed in mice fed by chow with or without 1.2% Lactobacillus powder after burn injury. Lamina propria mononuclear cells were enzymatically isolated from the ileum removed on 11th day post burn and incubated along with 1 μg/mL LPS or 10 μg/mL anti-CD3 antibody for 24 h; subsequently, the following seven cytokines were analyzed in the supernatant: IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, and IL-17. Results: Lactobacillus treatment post-burn injury markedly improved survival after lethal endotoxemia in burn-primed mice (64.3% vs. 21.4%, p = 0.03). The production of proinflammatory cytokines such as TNF-α, IL-6, and IL-17 by lamina propria mononuclear T-lymphocytes and macrophages including Th17 response was augmented by burn injury but decreased with Lactobacillus treatment after burn injury. Conclusions: Th17- and Th17-mediated inflammatory responses in the gut mucosa may play a vital role, which could be attenuated by Lactobacillus treatment, in survival of lethal endotoxemia in burn-primed mice.

LPS induces apoptosis in macrophages mostly through the autocrine production of TNF-α

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3823-3831 ◽  
Author(s):  
Jordi Xaus ◽  
Mònica Comalada ◽  
Annabel F. Valledor ◽  
Jorge Lloberas ◽  
Francisco López-Soriano ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Endotoxic Shock ◽  
Late Phase ◽  
No Synthase ◽  
Tnf Receptor ◽  
Tnf Receptors ◽  
Tnf Α ◽  
Early Apoptosis ◽  
Induced Apoptosis ◽  
Necrosis Factor

Abstract The deleterious effects of lipopolysaccharide (LPS) during endotoxic shock are associated with the secretion of tumor necrosis factor (TNF) and the production of nitric oxide (NO), both predominantly released by tissue macrophages. We analyzed the mechanism by which LPS induces apoptosis in bone marrow-derived macrophages (BMDM). LPS-induced apoptosis reached a plateau at about 6 hours of stimulation, whereas the production of NO by the inducible NO-synthase (iNOS) required between 12 and 24 hours. Furthermore, LPS-induced early apoptosis was only moderately reduced in the presence of an inhibitor of iNOS or when using macrophages from iNOS -/-mice. In contrast, early apoptosis was paralleled by the rapid secretion of TNF and was almost absent in macrophages from mice deficient for one (p55) or both (p55 and p75) TNF-receptors. During the late phase of apoptosis (12-24 hours) NO significantly contributed to the death of macrophages even in the absence of TNF-receptor signaling. NO-mediated cell death, but not apoptosis induced by TNF, correlated with the induction of p53 and Bax genes. Thus, LPS-induced apoptosis results from 2 independent mechanisms: first and predominantly, through the autocrine secretion of TNF- (early apoptotic events), and second, through the production of NO (late phase of apoptosis).

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