Role of TNF Alpha in Rheumatoid Arthritis

1. TNF Alpha and Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease involving multiple inflammatory mediators, including tumor necrosis factor alpha (TNF-α). TNF-α, a crucial inflammatory mediator, is a monocyte-derived cytokine primarily produced by monocytes and macrophages, playing an important role in immune responses by regulating inflammation and activation of immune cells. Its precursor is a type II transmembrane protein (mTNF-α). By binding to two receptors, TNFR-1 and TNFR-2, it triggers their activation and trimerization, resulting in a cascade of signal transduction pathways that affect cell survival and apoptosis. In RA patients, TNF-α levels are significantly increased and closely associated with disease severity and progression of arthritis.

Rheumatoid Arthritis

2. TNF Alpha Signaling Pathway

TNF-α binds in trimeric form and forms clusters on high-affinity receptors densely present on most cell membranes to exert its effects. The ligand/receptor complexes are rapidly endocytosed via coated pits and ultimately degraded in secondary lysosomes. Upon binding to receptors, TNF-α can activate multiple signaling pathways including NF-κB pathway, MAPK (Mitogen-Activated Protein Kinase) pathway, and JNK (c-Jun N-terminal Kinase) pathway. In the NF-κB pathway, NF-κB binds to IκB proteins in an inactive state. TNF-α induces phosphorylation and degradation of IκB, releasing active NF-κB to enter the nucleus and regulate gene transcription. Additionally, TNF-α can activate the MAPK pathway including ERK1/2, JNK, and p38 MAPK. These kinases further regulate cell proliferation, apoptosis, and inflammatory responses. In certain circumstances, TNF-α induces cell apoptosis. This can occur through activation of apoptotic signaling pathways such as the Caspase cascade. The TNFR1/TRADD complex recruits FADD via death domains, activating Caspase-8 and subsequently Caspase-3, leading to DNA fragmentation and cell apoptosis. TNF-α induces expression of apoptotic initiators like Bid and Bax, activates Caspase-8, and induces tumor cell apoptosis. Moreover, TNF-α induces non-classical Caspase-dependent cell apoptosis, altering mitochondrial permeability, releasing cytochrome C, secreting ROS, and inducing tumor cell death.

3. Rheumatoid Arthritis Treatment

Given the significance of TNF-α in the pathogenesis of RA, inhibiting TNF-α has become one of the primary strategies for treating RA. Biological agents targeting TNF-α are widely employed in the treatment of RA, including TNF-α inhibitors such as corticosteroids and anti-TNF-α biological agents (such as infliximab, etanercept, and adalimumab). By inhibiting the action of TNF-α, these medications can alleviate inflammation, improve joint function, and slow disease progression, thereby providing long-term clinical benefits for RA patients.

4. Recommended ELISA Kits

FineTest provides TNF-α ELISA kits with high specificity, which are suitable for rheumatoid arthritis research.

4.1. Humanized Antibody Drug

Catalogue No.

Product Name

Detection Range

Sensitivity

EU2616

Rituximab antibody ELISA Kit

1.563-100ng/ml

0.938ng/ml

EH4080

Human anti-TNF-α Antibody(Anti Tumor Necrosis Factor Alpha Antibody)

ELISA Kit

1.563-100ng/ml

0.938ng/ml

EU3589

Infliximab ELISA Kit

0.313-20ng/ml

0.188ng/ml

EU3590

Anti-Infliximab antibody ELISA Kit

1.563-100ng/ml

0.938ng/ml

EH5122

Human Golimumab ELISA Kit

0.625-40ng/ml

0.375ng/ml

EH5109

Human anti-Golimumab ELISA Kit

0.312-20ng/ml

0.188ng/ml

EH5106

Human Adalimumab ELISA Kit

1.563-100ng/ml

0.938ng/ml

EH5107

Human Anti-Adalimumab antibody ELISA kit

1.563-100ng/ml

0.938ng/ml

4.2. Species Category

Catalogue No.

Product Name

Detection Range

Sensitivity

EH0302

Human TNF-α(Tumor Necrosis Factor Alpha) ELISA Kit

15.625-1000pg/ml

9.375pg/ml

EH0302-HS

Human HS-TNF-α(High sensitive Tumor Necrosis Factor Alpha) ELISA Kit

3.12-200pg/ml

1.875pg/ml

EM0183

Mouse TNF-α(Tumor Necrosis Factor Alpha) ELISA Kit

3.906-250pg/ml

2.344pg/ml

EM0183-HS

Mouse TNF-α(High sensitive Tumor Necrosis Factor Alpha)ELISA Kit

1.563-100pg/ml

0.938pg/ml

ER1393

Rat TNF-α(Tumor Necrosis Factor Alpha) ELISA Kit

3.906-250pg/ml

2.344pg/ml

EP0159

Pig TNF-α (Tumor Necrosis Factor Alpha) ELISA Kit

31.25-2000pg/ml

18.75pg/ml

ECH6394

Chicken TNF-α (Tumor Necrosis Factor Alpha)ELISA kit

15.625-1000pg/ml

9.375pg/ml

EB0008

Bovine TNF-α(Tumor necrosis factor alpha) ELISA Kit

15.625-1000pg/ml

9.375pg/ml

EHS0006

Horse TNF-α(Tumor Necrosis Factor Alpha) ELISA Kit

15.625-1000pg/ml

9.375pg/ml

ERB0126

Rabbit TNF-α(Tumor Necrosis Factor Alpha) ELISA Kit

7.813-500pg/ml

4.688pg/ml

EMK0079

Monkey TNF-α(Tumor Necrosis Factor Alpha) ELISA Kit

31.25-2000pg/ml

18.75pg/ml

REFERENCES

[1] Additive efficacy of a bispecific anti-TNF/IL-6 nanobody compound in translational models of rheumatoid arthritis, PMID: 36724239.
[2] TNF-α versus IL-6 Genes Expression levels in Active Rheumatoid Arthritis: Clinical and Laboratory Determinants, PMID: 37787680.

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