scholarly journals Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Kathryn S. Brown ◽  
Huiyu Gong ◽  
Mark R. Frey ◽  
Brock Pope ◽  
Matthew Golden ◽  
...  
Keyword(s):  
Small Intestine ◽  
Tumor Necrosis Factor ◽  
Premature Infants ◽  
Tumor Necrosis ◽  
Intestinal Tract ◽  
Structural Changes ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Unique Challenge ◽  
Necrosis Factor

Background. Premature infants are commonly subject to intestinal inflammation. Since the human small intestine does not reach maturity until term gestation, premature infants have a unique challenge, as either acute or chronic inflammation may alter the normal development of the intestinal tract. Tumor necrosis factor (TNF) has been shown to acutely alter goblet cell numbers and villus length in adult mice. In this study we tested the effects of TNF on villus architecture and epithelial cells at different stages of development of the immature small intestine.Methods. To examine the effects of TNF-induced inflammation, we injected acute, brief, or chronic exposures of TNF in neonatal and juvenile mice.Results. TNF induced significant villus blunting through a TNF receptor-1 (TNFR1) mediated mechanism, leading to loss of villus area. This response to TNFR1 signaling was altered during intestinal development, despite constant TNFR1 protein expression. Acute TNF-mediated signaling also significantly decreased Paneth cells.Conclusions. Taken together, the morphologic changes caused by TNF provide insight as to the effects of inflammation on the developing intestinal tract. Additionally, they suggest a mechanism which, coupled with an immature immune system, may help to explain the unique susceptibility of the immature intestine to inflammatory diseases such as NEC.

Tumor Necrosis Factor as Mediator of Inflammatory Diseases and its Therapeutic Targeting: A Review

2013 ◽  
Vol 13 (4) ◽  
pp. 226-235 ◽  
Author(s):  
Kuldeep Dhama ◽  
Shyma K. Latheef ◽  
Hari Abdul Samad ◽  
Sandip Chakrabort ◽  
Ruchi Tiwari ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Inflammatory Diseases ◽  
Therapeutic Targeting ◽  
Necrosis Factor

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 Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 539
Author(s):  
Bahez Gareb ◽  
Antonius T. Otten ◽  
Henderik W. Frijlink ◽  
Gerard Dijkstra ◽  
Jos G. W. Kosterink
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Genetically Modified Organisms ◽  
Intestinal Inflammation ◽  
Systemic Exposure ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by intestinal inflammation. Increased intestinal levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) are associated with disease activity and severity. Anti-TNF-α therapy is administered systemically and efficacious in the treatment of IBD. However, systemic exposure is associated with adverse events that may impede therapeutic treatment. Clinical studies show that the efficacy correlates with immunological effects localized in the gastrointestinal tract (GIT) as opposed to systemic effects. These data suggest that site-specific TNF-α inhibition in IBD may be efficacious with fewer expected side effects related to systemic exposure. We therefore reviewed the available literature that investigated the efficacy or feasibility of local TNF-α inhibition in IBD. A literature search was performed on PubMed with given search terms and strategy. Of 8739 hits, 48 citations were included in this review. These studies ranged from animal studies to randomized placebo-controlled clinical trials. In these studies, local anti-TNF-α therapy was achieved with antibodies, antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and genetically modified organisms. This narrative review summarizes and discusses these approaches in view of the clinical relevance of local TNF-α inhibition in IBD.

Challenges in Diagnosing Latent Tuberculosis Infection in Patients Treated with Tumor Necrosis Factor Antagonists

2011 ◽  
Vol 38 (7) ◽  
pp. 1234-1243 ◽  
Author(s):  
EDWARD C. KEYSTONE ◽  
KIM A. PAPP ◽  
WENDY WOBESER
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Latent Tuberculosis Infection ◽  
Inflammatory Diseases ◽  
Diagnostic Testing ◽  
False Negative ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
Tnf Α ◽  
Necrosis Factor

Reactivation of latent tuberculosis infection (LTBI) is well recognized as an adverse event associated with anti-tumor necrosis factor-α (anti-TNF-α) therapy. The strengths and weaknesses of current techniques for detecting LTBI in patients with chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriasis have not been fully examined. T cell hyporesponsiveness due to immunosuppression caused by illness or drugs, referred to as anergy, may produce false-negative tuberculin skin test (TST) and interferon-γ release assay (IGRA) results. The literature suggests that anergy may influence screening performance of TST and IGRA tests in candidates for anti-TNF-α therapy. Conversely, the potential for false-positive TST and IGRA results must be considered, as treatment for LTBI may be associated with significant morbidity. This review examines the reliability issues related to LTBI diagnostic testing and provides practical direction to help prevent LTBI reactivation and facilitate successful anti-TNF-α treatment.

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