IL-8/CXCL8 蛋白, Human (CHO)

Interleukin-8 (IL-8), also known as CXCL8 or NAP-1, is a pro-inflammatory CXC chemokine. IL-8 acts on human neutrophils via two receptors, CXCR1 and CXCR2. IL-8 has a conserved Glu-Leu-Arg (ELR) N-terminal motif, and is an agonist for CXCR1/CXCR2. IL-8 is produced by various cells including leukocytes, endothelial cells, and epithelial cells^[1][2][3]. IL-8/CXCL8 Protein, Human (CHO) is produced in CHO cells, and consists of 77 amino acids (A23-S99).

IL-8 (CXCL8) 属于 ELR⁺ CXC 趋化因子家族。IL-8 最初产生为 99 个氨基酸的蛋白质，经过裂解形成活性 IL-8 同工型、非免疫细胞中的 77 个氨基酸肽或单核细胞和巨噬细胞中的 72 个氨基酸肽。编码IL-8的基因位于染色体4q13-q21上。IL-8 的二聚化形成了受体结合的结构基础。IL-8 由单核细胞、巨噬细胞、白细胞、内皮细胞和上皮细胞等多种细胞表达^[1][2][3]。
成熟的人IL-8/CXCL8与犬IL-8/CXCL8具有75%的氨基酸序列同一性。而人 IL-8 与恒河猴 IL-8 蛋白具有 94.95% 的氨基酸序列同一性。
IL-8 负责将中性粒细胞和粒细胞募集和激活至炎症部位。IL-8 在生理状态下几乎检测不到，但会被促炎细胞因子（例如 TNFα 和 IL-1β）快速诱导。IL-8的功能主要依赖于其与特定细胞表面GPCR、CXCR1和CXCR2的相互作用。此外，据报道，IL-8 可通过激活 PI3K/Akt 通路促进整合素 β3 上调和肝细胞癌细胞的侵袭。在牙源性病变中，IL-8已被证明在成釉细胞瘤上皮细胞和不可逆性牙髓炎中高表达。在类风湿性关节炎和其他炎症性关节疾病中，IL-8 可能导致中性粒细胞积聚，而中性粒细胞被认为是软骨降解酶的主要来源。IL-8 刺激细胞蛋白的 MAPK 和酪氨酸磷酸化。肿瘤细胞和成纤维细胞相互沟通，包括自分泌和旁分泌因子（包括 IL-8），导致 MMP2 和 MMP9 可降解细胞外基质 (ECM) 成分上调，从而触发肿瘤侵袭^[1]< support>[2]^[3][4]。
IL-8 通常已知可促进血管生成，但它也会激活基质金属蛋白酶（MMP）参与转移相关的组织重塑。IL-8 在脂多糖 (LPS) 刺激的单核细胞中被诱导，并显示出诱导中性粒细胞迁移。IL-8对肿瘤细胞的增殖、侵袭和迁移等生物学活性发挥多种作用。IL-8 还可增加雄激素非依赖性前列腺癌 (AIPC) 细胞系中 Akt 的表达。IL-8 通过中性粒细胞中的 PI3K 激活 MAPK 信号传导，并通过 EGFR 反式激活激活卵巢和肺癌细胞系中的 Ras-GTPase。大量实验数据表明，IL-8 和受体有助于消除病原体，但也可能对疾病相关过程产生显着影响，包括组织损伤、纤维化、血管生成和肿瘤发生^{[3] [5]}。

Recombinant human IL-8 (10, 30, and 100 μg/kg; single intravenous injection) injected into rhesus monkeys (2-3 years; 2.5-4.5 kg). IL-8 injection results in instant neutropenia that was due to pulmonary sequestration. Within 30 minutes after IL-8 injection, neutrophilia developed with counts up to 10-fold greater than baseline levels. The numbers of hematopoietic progenitor cells (HPCs) increased of blood at 30 minutes after injection of 100 μg/kg IL-8^[7].

Recombinant human IL-8/CXCL8 (100 ng/mL; for 24-96 h) stimulation leads to enhancement of invasion and suppression of late stage apoptosis in MG-63 cells. Moreover, secretions of MMPs by MG-63 cells are also increased upon stimulation. CXCL8 induces the elevations of phosphorylated PI3K and Akt, but not PKC or FAK^[6].

1. The ED₅₀ is <10 ng/mL as measured by CHO/Gα15 cells.
2. Measured in a cell proliferation assay using HUVEC human umbilical vein endothelial cells. The ED₅₀ for this effect is 1.656 ng/mL, corresponding to a specific activity is 6.039×10⁵ units/mg.

• 
  Measured in a cell proliferation assay using HUVEC human umbilical vein endothelial cells.The ED₅₀ for this effect is 1.656 ng/mL, corresponding to a specific activity is 6.039×10⁵ units/mg.

Human

CHO

Tag Free

P10145 (A23-S99)

3576  [NCBI]

AVLPRSAKELRCQCIKTYSKPFHPKFIKELRVIESGPHCANTEIIVKLSDGRELCLDPKENWVQRVVEKFLKRAENS

Approximately 12.5 kDa

• 
  Greater than 95% as determined by reducing SDS-PAGE.

无菌粉末.

Lyophilized from a 0.2 μm filtered solution of PBS or 20 mM PB, 150 mM NaCl, pH 7.4.

<0.2 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

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]. M Baggiolini, et al. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045-9.  [Content Brief]

  [2]. Baggiolini M, et al. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045-9.  [Content Brief]

  [3]. M Wolf, et al. Granulocyte chemotactic protein 2 acts via both IL-8 receptors, CXCR1 and CXCR2. Eur J Immunol. 1998 Jan;28(1):164-70.  [Content Brief]

  [4]. Koch AE, et al. Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science. 1992 Dec 11;258(5089):1798-801.  [Content Brief]

  [5]. Qian Liu, et al. The CXCL8-CXCR1/2 pathways in cancer. Cytokine Growth Factor Rev. 2016 Oct;31:61-71.  [Content Brief]

  [6]. Jian-Feng Liu, et al. IL-8 Is Upregulated in the Tissue-Derived EVs of Odontogenic Keratocysts. Biomed Res Int. 2022 Jul 30;2022:9453270.  [Content Brief]

  [7]. Remo C Russo, et al. The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases. Expert Rev Clin Immunol. 2014 May;10(5):593-619.  [Content Brief]

  [8]. Hai Jiang, et al. CXCL8 promotes the invasion of human osteosarcoma cells by regulation of PI3K/Akt signaling pathway. APMIS. 2017 Sep;125(9):773-780.  [Content Brief]

  [9]. L Laterveer, et al. Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a single intravenous injection of interleukin-8. Blood. 1996 Jan 15;87(2):781-8.  [Content Brief]