Creative Biolabs is one of the leading custom antibody generation and development providers. We specialize in the generation of antibodies against a wide range of targets for R&D, diagnostic, and therapeutic applications. Currently, we have launched a series of in vitro diagnostic (IVD) antibody development services targeting numerous diagnostic biomarkers of human diseases. Here, we focus on the tumor necrosis factor (TNF) as a marker of sepsis.

Tumor Necrosis Factor (TNF)

TNF, also known as troponin, is an inflammatory mediator. It is mainly produced by macrophages and can be induced by a variety of stimuli, such as IPS and immune complex viruses. The TNF produced by macrophages is named as TNF-α, the lymphotoxin produced by T lymphocytes is named TNF-β. Although TNF-α shares only about 30% homology with TNF-β, they share common receptors. The biological activity of TNFα accounts for 70% to 95% of the total activity of TNF. Therefore, TNF is often referred to as TNF-α. TNF has a dual effect, with antibacterial, antiviral, and immunoregulatory functions at the right dose, and adversely affects the body when abnormally increased or decreased.

Crystal structure of TNF-α.Fig.1 Crystal structure of TNF-α.

TNF Marker of Liver Failure

The cytokine TNF-α is an important cytokine, exerting biological effects in different tissues and species at multiple levels. It is a proinflammatory cytokine that mediates hepatic inflammation, oxidative stress, and apoptosis or necrosis of liver cells. TNF-α is a pleiotropic monocyte-derived cytokine that has been associated with cancer progression, severe inflammatory diseases, and liver injury. In order to fulfill inflammatory reactions in the tissue, TNF-α binds to two distinct receptors: TNFR1 and TNFR2. While TNFR1 is expressed in almost all tissue, TNFR2 is expressed only on inflammatory cells. Once TNF-α ligates TNFR1 the TNF receptor-associated protein with death domain (TRADD) is recruited to the death domain of TNFR1.

Serum levels of TNF-α are significantly increased in fatty liver disease and are well correlated with the severity of liver disease. Plasma TNF-α levels also were significantly higher in patients with chronic hepatitis C, with liver cirrhosis, and hepatocellular carcinoma when compared to those with acute or mild chronic hepatitis C. Additionally, a positive correlation of soluble TNFR1 and soluble TNFR2 and disease progression were described in patients with chronic hepatitis C.

The trimeric TNF-α engagement of TNFR1 leads to cellular apoptosis or cell survival via the distinct complex signaling pathways. Fig.2 The trimeric TNF-α engagement of TNFR1 leads to cellular apoptosis or cell survival via the distinct complex signaling pathways. (Yun, 2015)

TNF Marker of Sepsis

During tissue injury, binding of PAMP to PRR results in the release of NF-κB from its complex that is inactive in I-B. NF-κB is an important intracellular protein that can translocate to the nucleus and causes the transcription of pro-inflammatory cytokine TNF. The pro-inflammatory cytokine TNF further activates neutrophils, causing the expression of cell-adherent cofactor β-integrin (CD-11) and β2 integrin (CD-18). Pro-inflammatory cytokines up-regulate the expression of integrin receptors on endothelial cells, such as intracellular adhesion molecules and vascular adhesion molecules, causing adhesion of neutrophils to endothelial cells. Activation of endothelial cells by pro-inflammatory cytokines also increases the production of nitric oxide (NO) via inducible nitric oxide synthase. Neutrophils result in further tissue damage through the production of reactive oxygen intermediates. The addition of NO to the reactive oxygen intermediate results in the formation of peroxynitrite, which further causes cell damage.

Antibody Development Services Targeting TNF Marker

In recent years, IVD technology is undergoing rapid development. IVD antibodies have been widely used in immunodiagnostic tools to aid in the diagnosis of various diseases, conditions, and infections. With years of experience and advanced technology, Creative Biolabs is able to provide a full range of high-quality and cost-effective biomarker-specific antibody development services. Especially, we help develop novel anti-TNF antibodies for your IVD projects. Having completed a number of IVD antibody generation and development projects, Creative Biolabs is confident to offer you the best products and services to promote your project a success.

If you are interested in our IVD antibody discovery services, please contact us for more details.

Reference

  1. Yun Dong, (2015) “Targeting of Tumor Necrosis Factor Alpha Receptors as a Therapeutic Strategy for Neurodegenerative Disorders” Antibodies 4(4), 369-408.

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