Cynomolgus IL-23 alpha & Mouse IL-12 beta Heterodimer Protein (HEK293, His)

IL-23 alpha and IL-12 beta are the IL-23p19 and IL-12p40 subunits, respectively, composing IL-23 via heterodimerization manner. IL-23 binds to a heterodimeric receptor composed of IL-12RB1 and IL-23R, activates the Jak-Stat signaling cascade, acts on memory CD4(+) T cells preferentially^[1]. IL-23 also involves in activation of several pathways including p38 MAPK or NF-κB and promotes the production of pro-inflammatory cytokines such as interleukin-17A/IL17A^[2]. Cynomolgus IL-23 alpha & Mouse IL-12 beta Heterodimer Protein is produced in HEK293 cells, with total length of 481 amino acids and a N-Terminal His-tag.

IL-23 alpha and IL-12 beta, also known as IL23p19 and IL12p40, respectively, and composing IL-23 in a heterodimerization manner, exerts proinflammatory effects and promotes angiogenesis^[1][5].
IL-23 belongs to the IL-12 cytokine family together with IL-12 p35/p40, IL-27 EBI3/p28 and IL-35 EBI3/p35, and is produced by various immune cells such as dendritic cells and macrophages upon Toll-like receptor signaling in tissues^[3].
IL-23 has a preference expression on memory CD4(+) T cells, and activates the Jak-Stat signaling cascade. IL-23 leads to IL-23 receptor phosphorylation and forms a docking site to trigger phosphorylation signal of STAT3 and STAT4^[1].
IL-23 is a key factor perpetuating Th17 cell activation and cytokine production by binding IL-23 receptor to produce Th17 cytokines such as IL17 A, IL-17 F and IL-22^[2].
IL-23 also acts function on natural killer cells, results interferon-γ secretion increasing and enhances antibody-dependent cellular cytotoxicity^[4].
The sequence of amino acids in IL-23 alpha proteins of cynomolgus shows high similarity with human (97.88%) and is very different from mouse (74.6%) and rat (79.37%)
IL-23 facilitates development of inflammation in numerous other models of immune pathology where IL-12 had previously been implicated, including models of arthritis,intestinal inflammation, and psoriasis^[6][7][8].

Cynomolgus IL-23R, His Tag immobilized on CM5 Chip can bind Cynomolgus IL-23 alpha&Mouse IL-12 beta, His Tag with an affinity constant of 2.36 nM as determined in SPR assay (Biacore T200).

Cynomolgus

HEK293

N-His

A0A2K5TLV4 (V22-P189)&P43432 (M23-S335)

102128555  [NCBI]&16160  [NCBI]

VPGGSSPAWAQCQQLSQKLCTLAWSAHPLVGHMDLREEGDEETTNDVPHIQCGDGCDPQGLRDNSQFCLQRIRQGLIFYEKLLGSDIFTGEPSLLPDSPVGQLHASLLGLSQLLQPEGHHWETQQIPSPSPSQPWQRLLLRFKILRSLQAFVAVAARVFAHGAATLSP&MWELEKDVYVVEVDWTPDAPGETVNLTCDTPEEDDITWTSDQRHGVIGSGKTLTITVKEFLDAGQYTCHKGGETLSHSHLLLHKKENGIWSTEILKNFKNKTFLKCEAPNYSGRFTCSWLVQRNMDLKFNIKSSSSSPDSRAVTCGMASLSAEKVTLDQRDYEKYSVSCQEDVTCPTAEETLPIELALEARQQNKYENYSTSFFIRDIIKPDPPKNLQMKPLKNSQVEVSWEYPDSWSTPHSYFSLKFFVRIQRKKEKMKETEEGCNQKGAFLVEKTSTEVQCKGGNVCVQAQDRYYNSSCSKWACVPCRVRS

22 ( Cynomolgus IL23 alpha)&40-50 (Mouse IL12 beta) kDa

Greater than 95% as determined by Tris-Bis PAGE.

Lyophilized powder.

Lyophilized from a 0.22 μm filtered solution of PBS, pH 7.4. Normally 8% trehalose is added as protectant before lyophilization.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O.

Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Oppmann B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000 Nov;13(5):715-25.  [Content Brief]

  [2]. Parham C, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol. 2002 Jun 1;168(11):5699-708.  [Content Brief]

  [3]. Neurath MF. IL-23 in inflammatory bowel diseases and colon cancer. Cytokine Growth Factor Rev. 2019 Feb;45:1-8.  [Content Brief]

  [4]. Teng MW, et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med. 2015 Jul;21(7):719-29.  [Content Brief]

  [5]. Li Y, et al. Regulation of Memory T Cells by Interleukin-23. Int Arch Allergy Immunol. 2016;169(3):157-62.  [Content Brief]

  [6]. Langowski JL, et al. IL-23 promotes tumour incidence and growth. Nature. 2006 Jul 27;442(7101):461-5.  [Content Brief]

  [7]. Murphy CA, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med. 2003 Dec 15;198(12):1951-7.  [Content Brief]

  [8]. Yen D, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006 May;116(5):1310-6.  [Content Brief]

  [9]. Chan JR, et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. J Exp Med. 2006 Nov 27;203(12):2577-87.  [Content Brief]

  [10]. Yago T, et al. IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenuates collagen-induced arthritis in rats. Arthritis Res Ther. 2007;9(5):R96.  [Content Brief]