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IL-4及IL-4受体蛋白

IL-4及IL-4受体蛋白
背景介绍
IL-4IL-14R信号通路示意图
https://doi.org/10, e13444.10.7717/peerj.13444
IL-4/IL-14R信号通路示意图
白细胞介素4(IL-4)是一种复合多功效的四α螺旋束I型细胞因子,主要由CD4+T淋巴细胞分泌,嗜酸性粒细胞、嗜碱性粒细胞、肥大细胞、CD8+Th细胞和自然杀伤细胞也是其潜在来源,在癌症中,IL-4也可由肿瘤细胞自身产生。IL-4是辅助T细胞(Th2)分化产生的关键细胞因子,控制B细胞的发育、存活和成熟并可诱导M2巨噬细胞分化介导过敏反应。
IL-4的受体复合物相对复杂,当IL-4与IL-4Rα结合后,IL-4Rα分别与γc或IL-13Rα1异二聚化,形成I型或II型IL-4受体复合物。IL-4Rα是IL-4与IL-13的共同受体,区别在于IL-4以高亲和力结合IL-4Rα,而IL-13则以较低亲和力结合IL-13Rα1,进而与IL-4Rα异二聚化形成高亲和力复合物。
稳定状态下,IL-4和IL-4R处于低水平表达,但在外界刺激和炎症作用下,IL-4/IL-4R发出信号,激活JAK激酶然后磷酸化STAT-6,磷酸化的STAT-6异二聚化,迁移到细胞核,并结合IL-4和IL-13应答基因的启动子,激活下游信号通路,促进肿瘤生长转移,诱发多种免疫性疾病如过敏性鼻炎,鼻窦炎,哮喘和湿疹等。近年来,IL-4Rα作为潜在的百亿市场药物靶点备受瞩目,靶向IL-4/IL-4Rα的信号通路以减弱IL-4诱导的信号传导在各种炎症及肿瘤疾病治疗中前景广阔。
靶向IL-4 Rα / IL-4 / IL-13的药物具有广泛的适应症
哮喘
(Asthmas)
哮喘(Asthmas)是一种复杂、持续的炎症性疾病。 Dupilumab是一种靶向IL-4Rα的人源单克隆抗体,其作用机理是特异性阻断了Ⅱ型IL-4R/IL-13R信号通路,抑制IL-4和IL-13的双重活性与STAT6的信号传导,并从源头抑制了随后参与T2炎症反应的一些特征分子的形成。
Dupilumab治疗哮喘的机制
https://doi.org/10.3390/vaccines10060974
Dupilumab治疗哮喘的机制
特异性皮炎
(Atopic dermatitis,AD)
特应性皮炎(AD)是以皮肤炎症、屏障功能障碍和慢性瘙痒为特征的疾病。越来越多的证据强调,AD是一种特异性个体中过度表达IL-13/IL-4信号的皮肤炎症,因此,靶向IL-13/IL-4-JAK-STAT6/STAT3轴是开发AD新药的一个有希望的策略。
AD治疗药物的作用机制
https://doi.org/10.3390/jcm9113741
AD治疗药物的作用机制
过敏性鼻炎
(Allergic rhinitis,AR)
过敏性鼻炎(AR)是免疫球蛋白E(IgE)介导的鼻粘膜炎症反应,可引起多种并发症,是严重影响居民生活质量的常见慢性疾病,Liang et.al(2020)研究发现,抑制IL-4/STAT6/GATA3信号通路可以减少IL-4分泌、血清IgE和气道粘液生成,有效改善过敏症状。
抑制IL-4/IL-4R信号可抑制过敏性鼻炎反应
https://doi.org/10.3389/fphar.2020.00291
抑制IL-4/IL-4R信号可抑制过敏性鼻炎反应
转移性肿瘤
(Metastatic tumors,MT)
IL-4R在许多上皮性癌症中过表达,是转移性肿瘤治疗的一个很有前途的靶点,IL-4/IL-4R信号轴是上皮癌细胞前转移表型的一个强启动子,上皮癌细胞上的IL-4/IL-4R信号轴直接影响肿瘤生物学的研究进程,靶向IL-4或IL-4R的药物以抑制转移性肿瘤生长是一种潜在治疗手段。
IL-4/IL-4R信号在上皮癌细胞和肿瘤微环境(TME)的通路
https://doi.org/10.1007/s10585-015-9747-9
IL-4/IL-4R信号在上皮癌细胞和肿瘤微环境(TME)的通路
产品优势
ACROBiosystems百普赛斯致力于加速生物药研发上市进程和服务于更好的临床应用,提供高质量高标准蛋白产品,已成功开发独具特色的多种属、多标签的IL-4 R alpha/ IL-4/ IL-13系列重组蛋白。

构象真实:由HEK293系统表达的重组蛋白更接近蛋白天然构象

种属齐全:覆盖Human、Mouse、Cynomolgus / Rhesus macaque 等种属

标签丰富:覆盖His & Avi Tag、His Tag、Fc Tag、Fc & Avi Tag 等多种标签

高生物活性:经ELISA、SPR、BLI验证,免费提供protocol

高纯度:经SDS-PAGE验证高于95%

高结构均一性:经SEC-MALS验证高于90%

产品列表
分子 货号 种属 产品描述 订购/预购
IL-4 R alpha ILR-H5221 Human Human IL-4 R alpha / CD124 Protein, His Tag (MALS verified)

订购

ILR-H82E9 Biotinylated Human IL-4 R alpha / CD124 Protein, Avitag™,His Tag (MALS verified)

订购

ILR-H5253 Human IL-4 R alpha / CD124 Protein, Fc Tag (MALS verified)

订购

ILR-H82F4 Biotinylated Human IL-4 R alpha / CD124 Protein, Fc,Avitag™ (MALS verified)

订购

ILR-M52H1 Mouse Mouse IL-4 R alpha / CD124 Protein, His Tag

订购

ILR-M5252 Mouse IL-4 R alpha / CD124 Protein, Fc Tag (MALS verified)

订购

ILR-C52H8 Cynomolgus / Rhesus macaque Cynomolgus / Rhesus macaque IL-4 R alpha / CD124 Protein, His Tag (MALS verified)

订购

ILR-C5258 Cynomolgus / Rhesus macaque IL-4 R alpha / CD124 Protein, Fc Tag

订购

IL-4 IL4-H4218 Human ActiveMax® Human IL-4 Protein, Tag Free

订购

IL4-H82E0 Biotinylated Human IL-4 Protein, Avitag™,His Tag (MALS verified)

订购

IL4-H52H9 Human IL-4 Protein, His Tag (MALS verified)

订购

IL4-M52H5 Mouse Mouse IL-4 Protein, His Tag

订购

IL4-C5259 Cynomolgus Cynomolgus IL-4 Protein, Fc Tag (MALS verified)

订购

IL-13 IL3-H52H4 Human Human IL-13 Protein, His Tag

订购

IL3-H5256 Human IL-13 Protein, Fc Tag

订购

IL3-H82E5 Biotinylated Human IL-13 Protein, His,Avitag™

订购

IL3-M5249 Mouse Mouse IL-13 Protein, His Tag

订购

IL3-C5249 Cynomolgus Cynomolgus IL-13 Protein, His Tag

订购

IL3-C52H4 Canine Canine IL-13 Protein, His Tag

订购

验证数据
高纯度和高结构均一性经SDS-PAGE和SEC-MALS验证
经电泳(SDS-PAGE)验证,Fc标签的ILR-H5253蛋白纯度高于95%
ILR-H5253

HumanI IL-4 R alpha, Fc Tag (Cat. No. ILR-H5253)on SDS-PAGE under reducing (R) condition. The gel was stained overnight with Coomassie Blue. The purity of the protein is greater than 95%.

经SEC-MALS验证, Fc标签的IL4-C5259蛋白纯度/结构均一性高于90%
IL4-C5259-M1

The purity of Cynomolgus IL-4, Fc Tag (Cat. No. IL4-C5259) is more than 90% and the molecular weight of this protein is around 85-115 kDa verified by SEC-MALS.

高生物活性经ELISA验证
经ELISA验证,IL-4(IL4-H4218)可与IL-4 R alpha (ILR-H82E9)特异性结合,线性区间为2-78 ng/mL
IL4-H4218-E1

Immobilized ActiveMax® Human IL-4, Tag Free (Cat. No. IL4-H4218)at 5 μL/mL (100 μL/well) can bind Biotinylated Human IL-4 R alpha, Avitag,His Tag (Cat. No. ILR-H82E9) with a linear range of 2-78 ng/mL (QC tested).

申请 Protocol

经ELISA验证,IL-4(IL4-H4218)可与IL-4 R alpha(ILR-H5253)特异性结合,线性区间为1-20ng/mL
IL4-H4218-E2

Immobilized ActiveMax® Human IL-4, Tag Free(Cat. No. IL4-H4218)at 5 μg/mL (100 μL/well) can bind Human IL-4 R alpha, Fc Tag (Cat. No. ILR-H5253) with a linear range of 1-20 ng/mL (Routinely tested).

申请 Protocol

亲和力经SPR和BLI验证
经SPR验证,IL-13 R alpha 1(IL1-H82E8)可与IL-13(IL3-H52H4) 特异性结合,亲和力常数为34.4 nM
IL3-H52H4-S1

Biotinylated Human IL-13 R alpha 1 Protein, His,Avitag (Cat. No. IL1-H82E8) captured on Biotin CAP-Series S Sensor Chip can bind Human IL-13,His Tag (Cat. No. IL3-H52H4) with an affinity constant of 34.4 nM. as determined in a SPR assay (Biacore 8K) (Routinely tested).

申请 Protocol

经BLI验证,IL-13(IL3-H82E5)可与IL-13 R alpha 2(IL2-H52H5)特异性结合,亲和力常数为6.31 nM
IL3-H82E5-B1

Loaded Biotinylated Human IL-13, His,Avitag (Cat. No. IL3-H82E5) on SA Biosensor, can bind Human IL-13 R alpha 2 , His Tag (Cat. No. IL2-H52H5)with an affinity constant of 6.31 nM as determined in BLI assay (ForteBio Octet Red96e) (Routinely tested).

申请 Protocol

相关参考文献
  • [1] Weng, S. Y., Wang, X., Vijayan, S., Tang, Y., Kim, Y. O., Padberg, K., ... & Schuppan, D. (2018). IL-4 receptor alpha signaling through macrophages differentially regulates liver fibrosis progression and reversal. EBioMedicine, 29, 92-103.https://doi.org/10.1016/j.ebiom.2018.01.028.
  • [2] Husna, S. M. N., Shukri, N. M., Ashari, N. S. M., & Wong, K. K. (2022). IL-4/IL-13 axis as therapeutic targets in allergic rhinitis and asthma. PeerJ, https://doi.org/10, e13444.10.7717/peerj.13444.
  • [3] Liang, K. L., Yu, S. J., Huang, W. C., & Yen, H. R. (2020). Luteolin attenuates allergic nasal inflammation via inhibition of interleukin-4 in an allergic rhinitis mouse model and peripheral blood from human subjects with allergic rhinitis. Frontiers in pharmacology, 11, 291..https://doi.org/10.3389/fphar.2020.00291.
  • [4] Bankaitis, K. V., & Fingleton, B. (2015). Targeting IL4/IL4R for the treatment of epithelial cancer metastasis. Clinical & experimental metastasis, 32(8), 847-856.https://doi.org/10.1007/s10585-015-9747-9.
  • [5] Moran, A., & Pavord, I. D. (2020). Anti-IL-4/IL-13 for the treatment of asthma: The story so far. Expert Opinion on Biological Therapy, 20(3), 283-294.https://doi.org/10.1080/14712598.2020.1714027.
  • [6] Furue, M. (2020). Regulation of skin barrier function via competition between AHR axis versus IL-13/IL-4‒JAK‒STAT6/STAT3 axis: pathogenic and therapeutic implications in atopic dermatitis. Journal of Clinical Medicine, 9(11), 3741.https://doi.org/10.3390/jcm9113741.
  • [7] Pelaia, C., Pelaia, G., Crimi, C., Maglio, A., Armentaro, G., Calabrese, C., ... & Vatrella, A. (2022). Biological Therapy of Severe Asthma with Dupilumab, a Dual Receptor Antagonist of Interleukins 4 and 13. Vaccines, 10(6), 974.https://doi.org/10.3390/vaccines10060974.

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