IL-6 Signaling Pathway

Abstract:  Interleukin-6(IL-6) is an important cytokine mainly produced by T cell and monocyte. It will be released during infection, tissue damage or inflammation, and also plays its role as proinflammatory cytokine and anti-inflammatory modulator. There are three types of IL-6 signaling pathway: classical signaling pathway, trans-signaling pathway and trans-presentation.

Keywords:  IL-6 signaling pathway, cytokine, inflammation, Interleukin-6

1. IL-6 Signaling Pathway

In classical signaling pathway, IL-6 first binds with its receptor IL-6R to form the complex. Then, the complex binds with gp130 protein on the cell membrane, evoking the downstream signaling pathway and gene expression via activating intracellular signal transduction.

IL-6R exists in the soluble form. The binding affinity between SIL-6R and IL-6(IL-6R) is similar. The conjugate binds with gp130 to activate intracellular signal transduction.

Trans-presentation mainly happens in the antigen-specific interaction between dendritic cells offering IL-6 signaling and T cell receiving IL-6. IL-6 binds with IL-6 receptor in dendritic cells. The complex is transferred to plasma membrane and recognize T cell to phosphorylate STAT3 in the gp130 mediated T cell.

2. IL-6 in Inflammation Immunity and Disease

IL-6 has wide effects in inflammation, immune reaction and hematopoiesis. Role of IL-6 in hepatocyte induces the production of acute phase protein, e.g. C-reactive protein(CRP), complement C3, serum amyloid protein A(SAA), fibrinogen, thrombopoietin, hepcidin, haptoglobin, alpha-1-antichymotrypsin. Thus, IL-6 becomes the important mediator during acute phase response. However, higher concentration of SAA in the serum may cause severe complication, e.g. amyloidosis of amyloid protein A. Besides, IL-6 induced hepcidin production blocks the role of ferroportin 1 in intestine. The decrease of iron level in the serum causes chronic inflammation related iron deficiency anemia and anaemia. During hematopoiesis, IL-6 promotes the differentiation of hemopoietic stem cell, mature of megakaryocyte and release of blood platelet.

In the adaptive immune response, IL-6 also produces and induces the differentiation of CD4+ T cell into effector T cell via stimulating antibodies. Besides, IL-6 helps T cell in cell differentiation, production of IL-21 and regulation of immunoglobulin synthesis.

IL-6 induces bone marrow stromal cells to produce RANKL, promoting activation of osteoblast to increase angiogenesis and vascular permeability. IL-6 promotes coagulation cascade via inducing tissue factor, and improves vascular permeability of vascular endothelial cell. Besides, IL-6 accelerates vascular reactivity via increasing the expression of C5a receptor, possibly resulting in various pathological process, e.g. vasoconstriction and myocardial dysfunction.

3. IL-6 Clinical Trial

IL-6 is involved in the generation and development of various diseases. Its blood level is closely related to inflammation, virus infection and autoimmune diseases. In inflammatory response, the increase of IL-6 appears earlier than other factors(even earlier than CRP and PCT), and continues for a long time, thus assisting to early diagnosis of acute infection. Besides, IL-6 can be also applied in evaluating the severity of infection and prognosis. When the level of IL-6 is higher than 1000μg/L, prognosis is poor. However, the specificity of IL-6 is lower than PCT. PCT and CRP can compensate for its deficiencies.

4. Recommended Products

4.1. Recombinant Proteins

Cat.No

Product Name

M.W.

Host

P0174

Recombinant Human IL-6

20 kDa

E.Coli

P1832

Recombinant Human IL-6R

47.9 kDa

E.Coli

P4598

Recombinant Mouse IL-6

20.5 kDa

E.Coli

P1479

Recombinant hamster IL-6

23.5 kDa

E.Coli

P0271

Recombinant Goat IL-6

22.3 kDa

E.Coli

P0280

Recombinant Canine IL-6

22.8 kDa

E.Coli

P0172

Recombinant Bovine IL-6

20.6 kDa

E.Coli

P0173

Recombinant Chicken IL-6

22 kDa

E.Coli

P0175

Recombinant Porcine IL-6

20.8 kD

E.Coli

4.2. Antibodies

Cat.No

Product Name

M.W.

Antibody Type

Applications

FNab10638

IL6 antibody

24 kDa

Mouse mAb

ELISA, WB

FNab04284

IL6R antibody

80 kDa

Rabbit pAb

ELISA, WB, IHC, IP

4.3. ELISA Kits

Cat.No

Product Name

Range

Sensitivity

QT-EH0201

Human IL-6 QuickTest ELISA Kit

0.46-30pg/ml

0.28pg/ml

RTU-EH0201

Human IL-6 ELISA Kit

0.313-20pg/ml

0.188pg/ml

EH0201

Human IL-6 ELISA Kit

4.688-300pg/ml

2.813pg/ml

AQ-H0201-B

Human HS-IL-6 Accquant ELISA Kit

0.078-5pg/ml

0.046pg/ml

AQ-H0201

Human HS-IL-6 Accquant ELISA Kit

0.46-30pg/ml

0.28pg/ml

EH5092

Human anti-IL-6 antibody Elisa kit

3.125-200ng/ml

1.875ng/ml

QT-EM0121

Mouse IL-6 QuickTest ELISA Kit

3.125-200pg/ml

1.875pg/ml

EM0121

Mouse IL-6 ELISA Kit

15.625-1000pg/ml

9.375pg/ml

EM0121-HS

Mouse IL-6 ELISA Kit

6.25-400pg/ml

3.75pg/ml

AQ-M0121-B

Mouse HS-IL-6 Accquant ELISA Kit

6.25-400pg/ml

3.75pg/ml

ER0042

Rat IL-6 ELISA Kit

62.5-4000pg/ml

37.5pg/ml

ER1105

Rat IL-6R ELISA Kit

78.125-5000pg/ml

46.875pg/ml

QT-EMK0041

Monkey IL-6 QuickTest ELISA Kit

0.313-20pg/ml

0.188pg/ml

RTU-EMK0041

Monkey IL-6 ELISA Kit

0.313-20pg/ml

0.188pg/ml

EMK0041

Monkey IL-6 ELISA Kit

31.25-2000pg/ml

18.75pg/ml

EDK0006

Duck IL-6 ELISA Kit

31.25-2000pg/ml

18.75pg/ml

EGP0070

Guinea pig IL-6 ELISA Kit

15.625-1000pg/ml

9.375pg/ml

EP0099

Porcine IL-6 ELISA Kit

31.25-2000pg/ml

18.75pg/ml

EHA0006

Hamster IL-6 ELISA Kit

7.813-500pg/ml

4.688pg/ml

EHA0006-HS

Hamster IL-6 ELISA Kit

1.563-100pg/ml

0.938pg/ml

ESH0019

Sheep IL-6 ELISA Kit

7.813-500pg/ml

4.688pg/ml

ERB0068

Rabbit IL-6 ELISA Kit

15.625-1000pg/ml

9.375pg/ml

EHS0002

Horse IL-6 ELISA Kit

3.125-200pg/ml

1.875pg/ml

ECH0046

Chicken IL-6 ELISA Kit

31.25-2000pg/ml

18.75pg/ml

ECA0013

Canine IL-6 ELISA Kit

31.25-2000pg/ml

18.75pg/ml

EB0028

Bovine IL-6 ELISA Kit

31.25-2000pg/ml

18.75pg/ml

REFERENCES

[1]Hesperidin inhibits lung fibroblast senescence via IL-6/STAT3 signaling pathway to suppress pulmonary fibrosis, PMID: 36736168.
[2]Genetic perturbation of IL-6 receptor signaling pathway and risk of multiple respiratory diseases, PMID: 38898459.

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