白细胞介素-8

白细胞介素-8（英语：Interleukin-8，简称为白介素-8或IL-8，亦称为趋化因子CXCL8）是巨噬细胞和上皮细胞等分泌的细胞因子^[1]。白细胞介素-8结合趋化因子受体白细胞介素-8受体α(IL8RA, 又叫CXCR1)和白细胞介素-8受体β(IL8RB, 又叫CXCR2)而对嗜中性粒细胞(neutrophils)有细胞趋化作用而实现其对炎症反应的调节^[2][1]。 白细胞介素-8还有很强的促血管生成作用。白细胞介素-8在小支气管炎^[3] 和囊性纤维化^[4] 的发病中起重要作用。

Interleukin 8
PDB rendering based on 1IL8.
有效结构 PDB 直系同源检索：PDBe, RCSB PDB查询代码列表 1ICW, 1IKL, 1IKM, 1IL8, 1ILP, 1ILQ, 1QE6, 1ROD, 2IL8, 3IL8
标识
代号	IL8; CXCL8; GCP-1; GCP1; LECT; LUCT; LYNAP; MDNCF; MONAP; NAF; NAP-1; NAP1
扩展标识	遗传学：146930 同源基因：47937 ChEMBL: 2157 GeneCards: IL8 Gene
基因本体论描述 分子功能 · interleukin-8 receptor binding · protein binding · chemokine activity 细胞成分 · extracellular region · extracellular space 生物过程 · angiogenesis · response to molecule of bacterial origin · cellular component movement · inflammatory response · immune response · activation of signaling protein activity involved in unfolded protein response · cell cycle arrest · signal transduction · G-protein coupled receptor signaling pathway · negative regulation of cell proliferation · calcium-mediated signaling · regulation of cell adhesion · neutrophil chemotaxis · endoplasmic reticulum unfolded protein response · receptor internalization · response to endoplasmic reticulum stress · intracellular signal transduction · neutrophil activation · cellular protein metabolic process · cellular response to fibroblast growth factor stimulus · regulation of retroviral genome replication · negative regulation of G-protein coupled receptor protein signaling pathway · embryonic digestive tract development · induction of positive chemotaxis · cellular response to lipopolysaccharide · cellular response to interleukin-1 · cellular response to tumor necrosis factor · positive regulation of neutrophil chemotaxis Sources: Amigo / QuickGO
RNA表达模式
更多表达数据
直系同源体
物种	人类	小鼠
Entrez	3576	n/a
Ensembl	ENSG00000169429	n/a
UniProt	P10145	n/a
mRNA序列	NM_000584	n/a
蛋白序列	NP_000575	n/a
基因位置	Chr 4: 74.61 – 74.61 Mb	n/a
PubMed查询	[1]	n/a
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临床意义

白细胞介素-8（IL-8）是炎症相关的关键介质，在中性粒细胞募集和脱颗粒过程中发挥重要作用。^[5] 例如，它被认为是牙龈炎^[6]和银屑病[Psoriasis]的促炎介质之一。

氧化应激可增加 IL-8 的分泌，从而导致炎症细胞的募集，并进一步诱导氧化应激介质的增加，使其成为局部炎症中的关键参数。^[7] 此外，IL-8 还被证明与肥胖有关。^[8]

IL-8 可能在结直肠癌中发挥作用，它可作为自分泌生长因子促进结肠癌细胞系的生长^[9]，或通过裂解基质金属蛋白酶分子促进细胞分裂和可能的迁移。^[10] 研究还表明，IL-8 通过诱导跨膜转运蛋白的表达，在恶性胸膜间皮瘤的化疗耐药性中起着重要作用。^[11]

如果孕妇体内 IL-8 水平较高，其子代患精神分裂症的风险增加。^[12]高水平的 IL-8 也被发现会降低精神分裂症患者对抗精神病药物的阳性反应率。^[13]

在精神分裂症、精神分裂症谱系障碍、双相情感障碍、重度抑郁障碍、自闭症谱系障碍、帕金森病、痴呆和多发性硬化症患者的脑脊液（CSF）中观察到 IL-8 水平升高。^[14] 相比之下，在曾经自杀未遂的个体中，CSF IL-8 水平显著降低，并且与自杀未遂者的焦虑症状呈负相关。^[14]

IL-8 还与囊性纤维化的病理过程有关。作为一种信号分子，IL-8 能够募集并引导中性粒细胞至肺上皮组织。由于气道中性粒细胞的过度刺激和功能异常，它们释放出多种促炎分子和蛋白酶，从而导致肺组织进一步受损。^[15]

某些苯二氮䓬类药物对腺苷 A2B 受体介导的人肥大细胞 IL-8 分泌具有抑制作用。一项 2013 年的研究表明，地西泮（Diazepam）、4′-氯二氮䓬（4′-chlorodiazepam）和氟硝西泮（Flunitrazepam）依次显著降低 NECA 诱导的 IL-8 产生，而氯硝西泮（Clonazepam）仅表现出轻微的抑制作用。^[16]

此外，IL-8 水平升高也与细支气管炎（Bronchiolitis）有关，后者是一种由病毒感染引起的常见呼吸道疾病。^[17][18]

参见

• 趋化因子
• CXCR1
• CXCR2

参考文献

1. Baggiolini, M.; Walz, A.; Kunkel, S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J. Clin. Invest. 84: 1045-1049, 1989.
2. Ahuja SK, Ozcelik T, Milatovitch A, Francke U, Murphy PM. Molecular evolution of the human interleukin-8 receptor gene cluster. Nat Genet. 1992 Sep;2(1):31-6.
3. Emi, M. et al., Association of diffuse panbronchiolitis with microsatellite polymorphism of the human interleukin 8 (IL-8) gene. J. Hum. Genet. 44: 169-172, 1999.
4. Srivastava, M. et al., Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells. Proc. Nat. Acad. Sci. 101: 7693-7698, 2004.
5. Harada A, Sekido N, Akahoshi T, Wada T, Mukaida N, Matsushima K. Essential involvement of interleukin-8 (IL-8) in acute inflammation. Journal of Leukocyte Biology. November 1994, 56 (5): 559–564. PMID 7964163. S2CID 8035653. doi:10.1002/jlb.56.5.559. （原始内容存档于2016-07-27）.
6. Haake, SK, Huang, GTJ: Molecular Biology of the host-Microbe Interaction in Periodontal Diseases (Selected Topics). In Newman, Takei, Carranza, editors: Clinical Periodontology, 9th Edition. Philadelphia: W.B.Saunders Co. 2002. page 162.
7. Vlahopoulos S, Boldogh I, Casola A, Brasier AR. Nuclear factor-kappaB-dependent induction of CXCL8 gene expression by tumor necrosis factor alpha: evidence for an antioxidant sensitive activating pathway distinct from nuclear translocation. Blood. September 1999, 94 (6): 1878–1889. PMID 10477716. S2CID 25974629. doi:10.1182/blood.V94.6.1878.418k03_1878_1889.
8. Sharabiani MT, Vermeulen R, Scoccianti C, Hosnijeh FS, Minelli L, Sacerdote C, Palli D, Krogh V, Tumino R, Chiodini P, Panico S, Vineis P. Immunologic profile of excessive body weight. Biomarkers. May 2011, 16 (3): 243–251. PMID 21506696. S2CID 36127785. doi:10.3109/1354750X.2010.547948.
9. Brew R, Erikson JS, West DC, Kinsella AR, Slavin J, Christmas SE. Interleukin-8 as an autocrine growth factor for human colon carcinoma cells in vitro. Cytokine. January 2000, 12 (1): 78–85. PMID 10623446. doi:10.1006/cyto.1999.0518.
10. Itoh Y, Joh T, Tanida S, Sasaki M, Kataoka H, Itoh K, Oshima T, Ogasawara N, Togawa S, Wada T, Kubota H, Mori Y, Ohara H, Nomura T, Higashiyama S, Itoh M. IL-8 promotes cell proliferation and migration through metalloproteinase-cleavage proHB-EGF in human colon carcinoma cells. Cytokine. March 2005, 29 (6): 275–282. PMID 15749028. doi:10.1016/j.cyto.2004.11.005.
11. Milosevic, V. et al. Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5.Int. J. Cancer, https://doi.org/10.1002/ijc.32419
12. Brown AS, Hooton J, Schaefer CA, Zhang H, Petkova E, Babulas V, Perrin M, Gorman JM, Susser ES. Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. The American Journal of Psychiatry. May 2004, 161 (5): 889–895. PMID 15121655. doi:10.1176/appi.ajp.161.5.889.
13. Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC. Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia. The Journal of Clinical Psychiatry. July 2004, 65 (7): 940–947. PMID 15291683. doi:10.4088/JCP.v65n0710.
14. Shkundin A, Halaris A. IL-8 (CXCL8) Correlations with Psychoneuroimmunological Processes and Neuropsychiatric Conditions. Journal of Personalized Medicine. 2024, 14 (5): 488. PMC 11122344 . PMID 38793070. doi:10.3390/jpm14050488 .
15. Reeves EP, Williamson M, O'Neill SJ, Greally P, McElvaney NG. Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis. American Journal of Respiratory and Critical Care Medicine. June 2011, 183 (11): 1517–1523. PMID 21330456. doi:10.1164/rccm.201101-0072oc.
16. Hoffmann K, Xifró RA, Hartweg JL, Spitzlei P, Meis K, Molderings GJ, von Kügelgen I. Inhibitory effects of benzodiazepines on the adenosine A(2B) receptor mediated secretion of interleukin-8 in human mast cells. European Journal of Pharmacology. January 2013, 700 (1–3): 152–158. PMID 23266380. doi:10.1016/j.ejphar.2012.12.003.
17. Bohmwald, Karen; Gálvez, Nicolás M. S.; Canedo-Marroquín, Gisela; Pizarro-Ortega, Magdalena S.; Andrade-Parra, Catalina; Gómez-Santander, Felipe; Kalergis, Alexis M. Contribution of Cytokines to Tissue Damage During Human Respiratory Syncytial Virus Infection. Frontiers in Immunology. 18 March 2019, 10: 452. PMC 6431622 . PMID 30936869. doi:10.3389/fimmu.2019.00452 .
18. Sacco, RE; McGill, JL; Palmer, MV; Lippolis, JD; Reinhardt, TA; Nonnecke, BJ. Neonatal calf infection with respiratory syncytial virus: drawing parallels to the disease in human infants.. Viruses. December 2012, 4 (12): 3731–53. PMC 3528288 . PMID 23342375. doi:10.3390/v4123731 .

外部链接

• Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006 Feb 9;354(6):610-21. （页面存档备份，存于互联网档案馆）