白细胞介素-8
白细胞介素-8(英語: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结合趨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。
临床意义
[编辑]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
[编辑]参考文献
[编辑]- ^ 1.0 1.1 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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).
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- ^ 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.
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