白血球介素-8
白血球介素-8(英語:Interleukin-8,簡稱為白介素-8或IL-8,亦稱為趨化因子CXCL8)是巨噬細胞和上皮細胞等分泌的細胞因子[1]。白血球介素-8結合趨化因子受體白血球介素-8受體α(IL8RA, 又叫CXCR1)和白血球介素-8受體β(IL8RB, 又叫CXCR2)而對嗜中性粒細胞(neutrophils)有細胞趨化作用而實現其對炎症反應的調節[2][1]。 白血球介素-8還有很強的促血管生成作用。白血球介素-8在小支氣管炎[3] 和囊性纖維化[4] 的發病中起重要作用。
臨床意義
[編輯]白血球介素-8(IL-8)是炎症相關的關鍵介質,在中性粒細胞募集和脫顆粒過程中發揮重要作用。[5] 例如,它被認為是牙齦炎[6]和銀屑病[Psoriasis]的促炎介質之一。
氧化應激可增加 IL-8 的分泌,從而導致炎症細胞的募集,並進一步誘導氧化應激介質的增加,使其成為局部炎症中的關鍵參數。[7] 此外,IL-8 還被證明與肥胖有關。[8]
IL-8 可能在結直腸癌中發揮作用,它可作為自分泌生長因子促進結腸癌細胞系的生長[9],或通過裂解基質金屬蛋白酶分子促進細胞分裂和可能的遷移。[10] 研究還表明,IL-8 通過誘導跨膜轉運蛋白的表達,在惡性胸膜間皮瘤的化療耐藥性中起著重要作用。[11]
如果孕婦體內 IL-8 水平較高,其子代患精神分裂症的風險增加。[12]高水平的 IL-8 也被發現會降低精神分裂症患者對抗精神病藥物的陽性反應率。[13]
在精神分裂症、精神分裂症譜系障礙、雙相情感障礙、重度抑鬱障礙、自閉症譜系障礙、帕金森病、痴呆和多發性硬化症患者的腦脊液(CSF)中觀察到 IL-8 水平升高。[14] 相比之下,在曾經自殺未遂的個體中,CSF IL-8 水平顯著降低,並且與自殺未遂者的焦慮症狀呈負相關。[14]
IL-8 還與囊性纖維化的病理過程有關。作為一種信號分子,IL-8 能夠募集並引導中性粒細胞至肺上皮組織。由於氣道中性粒細胞的過度刺激和功能異常,它們釋放出多種促炎分子和蛋白酶,從而導致肺組織進一步受損。[15]
某些苯二氮䓬類藥物對腺苷 A2B 受體介導的人肥大細胞 IL-8 分泌具有抑制作用。一項 2013 年的研究表明,地西泮(Diazepam)、4′-氯二氮䓬(4′-chlorodiazepam)和氟硝西泮(Flunitrazepam)依次顯著降低 NECA 誘導的 IL-8 產生,而氯硝西泮(Clonazepam)僅表現出輕微的抑制作用。[16]
此外,IL-8 水平升高也與細支氣管炎(Bronchiolitis)有關,後者是一種由病毒感染引起的常見呼吸道疾病。[17][18]
參見
[編輯]參考文獻
[編輯]- ^ 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.
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- ^ 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.
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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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