Cytokines
Product List
Recombinant Human Interleukin-2 protein (IL2) (Active)
Recombinant Human Interleukin-2/IL2 is produced through the expression of a DNA sequence encoding amino acids 21-153 of human IL2 in E. coli. The full-length mature protein exhibits a purity exceeding 97%, as determined by SDS-PAGE and HPLC analyses. Its biological activity is confirmed by its potent effect on cell proliferation in a murine CTLL-2 cell assay (ED50 < 0.1 ng/ml, specific activity > 1.0x107 IU/mg). The endotoxin content of this IL2 is less than 1.0 EU/µg, as determined by the LAL method. This recombinant IL2 protein is tag-free, but CUSABIO offers custom services to accommodate the need for specific tags. This recombinant IL2 protein is suitable for applications such as producing anti-IL2 antibodies and conducting immunology studies.
IL2 is a small α-helical cytokine that regulates immune cell homeostasis through IL2-IL2R signaling. It mediates activation-induced cell death (AICD) and consistently activates T-regulatory (Treg) cells. As a B-cell growth factor, IL2 stimulates antibody synthesis and facilitates the proliferation and differentiation of NK cells, enhancing their cytolytic functions. IL2 is also crucial for the development and survival of Treg cells, enabling them to play a significant role in controlling the immune response and influencing the pathogenesis of various pathological conditions, including cancer, metabolic disorders, infectious diseases, autoimmune diseases, and inflammatory diseases.
Recombinant Human Interleukin-6 protein (IL6) (Active)
Recombinant human IL6 is produced in E. coli by cloning the gene encoding amino acids 30-212 of human IL6 into an expression vector, which is then transformed into E. coli cells. These cells are cultured under conditions that promote protein expression. After reaching sufficient growth, the cells are lysed to release the recombinant IL6 protein. The obtained recombinant IL6 protein is then purified using affinity chromatography. The purity of the IL6 protein is confirmed using SDS-PAGE and exceeds 96%. Its endotoxin content is less than 1.0 EU/µg, as determined by the LAL method. This recombinant mouse IL6 protein has been validated to be active. Cell proliferation assays are performed to verify the protein's activity, ensuring its functional integrity post-purification.
IL6 acts in an autocrine manner to regulate basal cellular functions in human endothelial cells [1]. It is implicated in cell cycle regulation, signaling, and cellular movement [1]. IL6 also modulates gene expression in cellular responses mediated by cytokines and bacterial infections [2]. Studies have shown that IL6 is essential for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance [3].
IL6 has been shown to induce a signaling loop that activates the canonical WNT signaling pathway in pathological conditions, suggesting its potential as a target for diseases like rheumatoid arthritis and certain cancers [4]. IL6 autoantibodies are associated with the pathogenesis of type 2 diabetes [5]. Furthermore, IL6 is involved in inflammatory responses and metabolism [5]. It synergistically activates the transcription of inflammatory cytokines like interleukin-8 in conjunction with other transcription factors like NF-kappa B [6].
References:
[1] L. Ljungberg, M. Zegeye, C. Kardeby, K. Fälker, D. Repsilber, & A. Sirsjö, Global transcriptional profiling reveals novel autocrine functions of interleukin 6 in human vascular endothelial cells, Mediators of Inflammation, vol. 2020, p. 1-12, 2020. https://doi.org/10.1155/2020/4623107
[2] Y. Yang, V. Tesmer, & M. Bina, Regulation of HIV-1 transcription in activated monocyte macrophages, Virology, vol. 299, no. 2, p. 256-265, 2002. https://doi.org/10.1006/viro.2001.1530
[3] Y. Zhang, W. Yan, M. Collins, F. Bednar, S. Rakshit, B. Zetter et al., Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance, Cancer Research, vol. 73, no. 20, p. 6359-6374, 2013. https://doi.org/10.1158/0008-5472.can-13-1558-t
[4] M. Katoh and M. Katoh, Stat3-induced Wnt5a signaling loop in embryonic stem cells, adult normal tissues, chronic persistent inflammation, rheumatoid arthritis and cancer (review), International Journal of Molecular Medicine, 2007. https://doi.org/10.3892/ijmm.19.2.273
[5] K. Fosgerau, P. Galle, T. Hansen, A. Albrechtsen, C. Rieper, B. Pedersen et al., Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes, Journal of Endocrinology, vol. 204, no. 3, p. 265-273, 2009. https://doi.org/10.1677/joe-09-0413
[6] T. Matsusaka, K. Fujikawa, Y. Nishio, N. Mukaida, K. Matsushima, T. Kishimoto et al., Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8., Proceedings of the National Academy of Sciences, vol. 90, no. 21, p. 10193-10197, 1993. https://doi.org/10.1073/pnas.90.21.10193
Recombinant Human Interleukin-10 protein (IL10) (Active)
Recombinant human IL10 is produced in E. coli using a plasmid containing the gene fragment encoding amino acids 19-178 of human IL10. The protein exhibits a purity exceeding 95%, as determined by SDS-PAGE analysis, and an endotoxin level below 1.0 EU/µg, as measured by the LAL method. This recombinant human IL10 protein has been validated for biological activity. Its ED50, determined using a cell proliferation assay with murine MC/9-2 cells, is less than 1 ng/ml, indicating a specific activity greater than 1.0x10^6 IU/mg.
Human IL10 is a pivotal anti-inflammatory cytokine that orchestrates immune responses and maintains homeostasis within the immune system. Primarily synthesized by monocytes, lymphocytes, and mast cells, IL10 is renowned for its ability to suppress the production of pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 [1][2]. This inhibitory function is essential for controlling excessive inflammatory responses that could lead to tissue damage and chronic inflammatory diseases.
IL10 exerts its effects by binding to the IL10 receptor, initiating a signaling cascade involving the JAK and STAT pathways. This activation leads to the transcription of anti-inflammatory genes and the suppression of pro-inflammatory mediators [3]. Research has demonstrated that IL10 deficiency can augment Th1 and Th17 immune responses, associated with various autoimmune conditions [4].
Furthermore, IL10 has been implicated in diverse pathological conditions, including chronic inflammatory diseases and cancer. Its role in modulating macrophage activation and promoting a regulatory T cell phenotype is crucial in conditions such as endometriosis and atherosclerosis, where inflammation is a central component [5][6]. IL10 can influence tumor microenvironments by modulating immune cell functions, potentially suppressing or promoting tumor growth depending on the specific context [7].
References:
[1] Jung, K., Lee, G., Park, C., Lee, T., Kim, J., Sung, E., et al. (2020). Mesenchymal stem cells decrease oxidative stress in the bowels of interleukin-10 knockout mice. Gut and Liver, 14(1), 100-107. https://doi.org/10.5009/gnl18438
[2] Ōnishi, A., Akimoto, T., Urabe, M., Hirahara, I., Muto, S., Ozawa, K., et al. (2015). Attenuation of methylglyoxal-induced peritoneal fibrosis: immunomodulation by interleukin-10. Laboratory Investigation, 95(12), 1353-1362. https://doi.org/10.1038/labinvest.2015.110
[3] Verma, R., Balakrishnan, L., Sharma, K., Khan, A., Advani, J., Gowda, H., et al. (2015). A network map of interleukin-10 signaling pathway. Journal of Cell Communication and Signaling, 10(1), 61-67. https://doi.org/10.1007/s12079-015-0302-x
[4] Wang, S., Gao, X., Shen, G., Wang, W., Li, J., Zhao, J., et al. (2016). Interleukin-10 deficiency impairs regulatory t cell-derived neuropilin-1 functions and promotes th1 and th17 immunity. Scientific Reports, 6(1). https://doi.org/10.1038/srep24249
[5] Idrissi, F., Fruchart, M., Bélarbi, K., Lamer, A., Dubois-Deruy, E., Lemdani, M., et al. (2022). Exploration of the core protein network under endometriosis symptomatology using a computational approach. Frontiers in Endocrinology, 13. https://doi.org/10.3389/fendo.2022.869053
[6] Xu, J., Zhang, X., Rong, S., Gao, H., Yang, W., Li, J., et al. (2018). Yirui capsules alleviate atherosclerosis by improving the lipid profile and reducing inflammation in apolipoprotein e-deficient mice. Nutrients, 10(2), 142. https://doi.org/10.3390/nu10020142
[7] Lima, M., Quintans-Júnior, L., Santana, W., Kaneto, C., Soares, M., & Villarreal, C. (2013). Anti-inflammatory effects of carvacrol: evidence for a key role of interleukin-10. European Journal of Pharmacology, 699(1-3), 112-117. https://doi.org/10.1016/j.ejphar.2012.11.040
Recombinant Human Interleukin-11 protein (IL11) (Active)
The gene fragment encoding amino acids 22-199 of human IL11 is cloned into a vector and subsequently transfected into E. coli for expression. The resulting product is recombinant human IL11 protein. Its biological activity has been validated by a cell proliferation assay utilizing murine B9-11 cells, exhibiting an ED50 of < 1 ng/ml, corresponding to a specific activity exceeding 1.0x106 IU/mg. The protein purity is greater than 95% as determined by SDS-PAGE. Its endotoxin level is less than 1.0 EU/µg as measured by the LAL method.
Human IL11 is predominantly produced by a variety of cell types, including fibroblasts, macrophages, and endothelial cells. It exerts its biological effects through the gp130 receptor signaling pathway, which it shares with other cytokines within the same family, such as IL6 and leukemia inhibitory factor (LIF) [1][2].
IL11 is renowned for its anti-inflammatory properties and its ability to promote the proliferation and differentiation of hematopoietic progenitor cells, particularly megakaryocytes, which are crucial for platelet production [3][4]. Beyond hematopoiesis, IL11 is implicated in various pathological conditions, including cancer. Studies have revealed that IL11 can enhance the invasive properties of certain cancer cells, such as those found in gastric and colorectal carcinomas, suggesting its involvement in tumor progression and metastasis [5][6]. IL11 can also modulate the activity of immune cells, influencing their proliferation and differentiation, which has implications for autoimmune diseases and inflammatory conditions [7][8].
References:
[1] P. Paiva, L. Salamonsen, U. Manuelpillai, & E. Dimitriadis, Interleukin 11 inhibits human trophoblast invasion indicating a likely role in the decidual restraint of trophoblast invasion during placentation1, Biology of Reproduction, vol. 80, no. 2, p. 302-310, 2009. https://doi.org/10.1095/biolreprod.108.071415
[2] B. Sands, B. Winston, B. Salzberg, M. Safdi, C. Barish, L. Wrubleet al., Randomized, controlled trial of recombinant human interleukin‐11 in patients with active crohn's disease, Alimentary Pharmacology & Therapeutics, vol. 16, no. 3, p. 399-406, 2002. https://doi.org/10.1046/j.1365-2036.2002.01179.x
[3] Y. Xiao, J. Liu, X. Huang, J. Guo, P. Fu, X. Huanget al., A clinical study on juheli (recombinant human interleukin - 11) in the second prevention of chemotherapy induced thrombocytopenia, Asian Pacific Journal of Cancer Prevention, vol. 17, no. 2, p. 485-489, 2016. https://doi.org/10.7314/apjcp.2016.17.2.485
[4] S. Sun, W. Wang, Y. Latchman, D. Gao, B. Aronow, & J. Reems, Expression of plasma membrane receptor genes during megakaryocyte development, Physiological Genomics, vol. 45, no. 6, p. 217-227, 2013. https://doi.org/10.1152/physiolgenomics.00056.2012
[5] T. Nakayama, A. Yoshizaki, S. Izumida, T. Suehiro, S. Maeda, T. Uemuraet al., Expression of interleukin-11 (il-11) and il-11 receptor α in human gastric carcinoma and il-11 upregulates the invasive activity of human gastric carcinoma cells, International Journal of Oncology, 2007. https://doi.org/10.3892/ijo.30.4.825
[6] A. Yoshizaki, T. Nakayama, K. Yamazumi, Y. Yakata, M. Taba, & I. Sekine, Expression of interleukin (il)-11 and il-11 receptor in human colorectal adenocarcinoma: il-11 up-regulation of the invasive and proliferative activity of human colorectal carcinoma cells, International Journal of Oncology, 2006. https://doi.org/10.3892/ijo.29.4.869
[7] H. Elshabrawy, M. Volin, A. Essani, Z. Chen, I. McInnes, K. Raemdoncket al., Il-11 facilitates a novel connection between ra joint fibroblasts and endothelial cells, Angiogenesis, vol. 21, no. 2, p. 215-228, 2018. https://doi.org/10.1007/s10456-017-9589-y
[8] V. Lewis, M. Ozawa, M. Deavers, G. Wang, T. Shintani, W. Arapet al., The interleukin-11 receptor α as a candidate ligand-directed target in osteosarcoma: consistent data from cell lines, orthotopic models, and human tumor samples, Cancer Research, vol. 69, no. 5, p. 1995-1999, 2009. https://doi.org/10.1158/0008-5472.can-08-4845
Introduction
Interleukins (ILs) are a group of cytokines, which are secreted proteins and signal molecules primarily produced by leukocytes (white blood cells). They play a crucial role in the immune system by mediating communication between cells . The human genome encodes more than 50 interleukins and related proteins . Interleukins are classified based on their structure and function, with common families including IL-1, IL-2, IL-6, and IL-12 .
Key Biological Properties: Interleukins are biologically active glycoproteins derived primarily from activated lymphocytes and macrophages . They induce T-lymphocyte activation and proliferation, augment neutrophil, macrophage, and T-lymphocyte cytotoxicity, and promote B lymphocyte and multilineage bone marrow stem-cell precursor growth and differentiation .
Expression Patterns and Tissue Distribution: Interleukins are produced by various cell types, including immune cells like macrophages and lymphocytes . They are expressed in different tissues, such as the bone marrow, thymus, and other epithelial cells .
Primary Biological Functions: Interleukins modulate the growth, differentiation, and activation of immune cells during inflammatory and immune responses . They play a role in both innate and adaptive immune responses .
Role in Immune Responses and Pathogen Recognition: Interleukins are involved in the regulation of immune responses, inflammatory reactions, and hematopoiesis . They help coordinate the body’s response to infections, inflammation, and other immune challenges .
Mechanisms with Other Molecules and Cells: Interleukins interact with specific cell surface receptors to stimulate target cells . For example, IL-6 controls leucocyte recruitment, determines the activity and maintenance of the inflammatory infiltrate, and drives various innate and adaptive immune responses .
Binding Partners and Downstream Signaling Cascades: Interleukins bind to their respective receptors, triggering downstream signaling pathways such as the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways . These signaling cascades lead to various cellular responses, including proliferation, differentiation, and cytokine production .
Regulatory Mechanisms Controlling Expression and Activity: The expression and activity of interleukins are regulated by complex molecular mechanisms. For example, IL-10 production is regulated by metabolic pathways and molecular signals downstream of the IL-10 receptor .
Transcriptional Regulation and Post-Translational Modifications: Interleukins undergo transcriptional regulation and post-translational modifications to ensure proper function. These modifications can include phosphorylation, glycosylation, and cleavage .
Biomedical Research: Interleukins are extensively studied in biomedical research for their roles in immune regulation and disease pathogenesis .
Diagnostic Tools: Interleukins serve as biomarkers for various diseases, aiding in diagnosis and monitoring of disease progression .
Therapeutic Strategies: Interleukins are used in therapeutic strategies, such as cancer immunotherapy and treatment of autoimmune diseases . For example, engineered cytokines from the IL-2 family have shown significant effects in tumor immunotherapy .
Role Throughout the Life Cycle: Interleukins play essential roles throughout the life cycle, from development to aging and disease. They regulate hematopoiesis, immune responses, and inflammation . For instance, IL-5 regulates eosinophil proliferation and differentiation, while IL-1 is involved in inflammatory responses .
