背景介绍(Background)：

This protein is a subunit of interleukin 12, a cytokine that acts on T and natural killer cells and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kD cytokine receptor like subunit encoded by this gene, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children. [provided by RefSeq, Jul 2008]

 

Interleukin (IL) -12 is a heterodimer composed of a 35 kD α-chain (p35 subunit) and a 40 kD β-chain (p40 subunit), which are tied by disulphide-bonds. This pro-inflammatory cytokine produced by DCs, macrophages and B cells in response to microbial pathogens, induces IFNγ production by T cells and facilitates Th1 differentiation. IL-12 can also induce production of IFNγ by NK cells. Like IL-12, the IL-12 receptor (IL-12R) is composed of two different subunits, which are termed IL-12Rβ1 and IL-12Rβ2. Aggregation of β1- andβ2-chains leads to the formation of high-affinity binding sites.While IL-12Rβ1 interacts with the IL-12p40 subunit, IL-12p35 is mainly connecting with IL-12Rβ2. Signaling via the IL-12R essentially depends on JAKs. The JAK family members JAK2 and Tyk2 are associated with IL-12Rβ2 and IL-12Rβ1, respectively. While no specific role in IL-12 signal transduction is known for the latter, the former is transphosphorylated upon binding of IL-12 to IL-12R. In turn, phospho-JAK2 phosphorylates the tyrosine residue Y800 of IL12Rβ2, which subsequently acts as a binding site for STAT molecules, especially STAT4. STATs are phosphorylated by JAK2 as well and are then able to form homo- or heterodimers, which can translocate to the cell nucleus, where they operate as promotors or repressors of gene transcription. The IFN-γ gene was early identified as a target of STAT4.

Besides in infection, the role of IL-12 has been extensively studied in several animal models of human diseases （such as psoriasis, inflammatory bowel diseases, cancer） which are thought to arise from autoimmunity phenomenona and are at least in part characterized by an excessive TH1 response. Moreover, (co-)targeting of IL-12 is an established therapeutic approach in psoriasis today and other conditions are likely to follow.

In addition to IL-12, the IL-12 family includes IL-23, IL-27 and IL-35. This family is unique in comprising the only heterodimeric cytokines.

 

 

 

图 IL-12的分泌和信号转导

 

 

 

 

制剂(Formulation)：

Lyophilized from 0.22 μm filtered solution in PBS，5%mannital，0.01% Tween80 pH7.4. 

 

质量控制(Quality Control)：

Purity: ≥ 95% as determined by reducing SDS-PAGE.    

Endotoxin: ＜ 0.1 EU/ug  as determined by LAL test.

 

保存(Storage)：

Use a manual defrost freezer and avoid repeated freeze - thaw cycles.
12 months from date of receipt, -20 to -70℃ as supplied.
1 month, 2 to 8℃ under sterile conditions after reconstitution.
6 months, -20 to -70℃ under sterile conditions after reconstitution.

 

FOR RESEARCH USE ONLY

 

 

 

 

 

 

 

 

参考文献：

[1] Tait Wojno ED, et al. 2019. Immunity. 50(4):851-870.

[2] Zundler S, Neurath MF. 2015. Cytokine Growth Factor Rev. 26(5):559-68.

[3] Vignali DA, Kuchroo VK. 2012. Nat Immunol. 13(8):722-8.