Arachidonate 5-lipoxygenase (ALOX5)

  • 文章类型: Journal Article
    花生四烯酸酯5-脂氧合酶(ALOX5)是白三烯合成中的主要酶,它们是强大的免疫调节脂质介质。我们先前报道了ALOX5在人淋巴组织的地幔区的B淋巴细胞中优先表达。在生理相关性的背景下,小鼠中Alox5基因的丢失显着损害了滤泡B辅助性T细胞的发育和抗体的产生。然而,尚未详细研究B细胞淋巴瘤中ALOX5的表达。在这项研究中,我们使用市售的抗ALOX5抗体通过免疫组织化学检测了代表性B细胞淋巴瘤和非肿瘤性淋巴组织中的ALOX5表达,该抗体可用于福尔马林固定的石蜡包埋标本.有趣的是,22/22例套细胞淋巴瘤,7/7例慢性淋巴细胞白血病/小细胞淋巴瘤,20/20例滤泡性淋巴瘤表达ALOX5。结外边缘区淋巴瘤/粘膜相关淋巴组织淋巴瘤或淋巴结边缘区淋巴瘤病例中有一小部分ALOX5阳性(分别为2/13或1/3)。相比之下,无弥漫性大B细胞淋巴瘤,无论生发中心B细胞(GCB)或非GCB类型,表达ALOX5(0/25例)。这些发现表明ALOX5可能是鉴定B细胞淋巴瘤起源细胞的新标记。需要进一步研究以阐明ALOX5在淋巴瘤细胞中表达的生物学意义。
    Arachidonate 5-lipoxygenase (ALOX5) is a cardinal enzyme in the synthesis of leukotrienes, which are powerful immune-regulating lipid mediators. We previously reported that ALOX5 is preferentially expressed in B lymphocytes in the mantle zone of human lymphoid tissue. In the context of physiological relevance, the loss of the Alox5 gene in mice significantly impairs the development of follicular B helper T cells and antibody production. However, ALOX5 expression in B-cell lymphomas has not been investigated in detail. In this study, we examined ALOX5 expression in representative B-cell lymphomas and non-neoplastic lymphoid tissues by immunohistochemistry with a commercially available anti-ALOX5 antibody that can be used on formalin-fixed paraffin-embedded specimens. Interestingly, 22/22 cases of mantle cell lymphoma, 7/7 cases of chronic lymphocytic leukemia/small cell lymphoma, and 20/20 cases of follicular lymphoma expressed ALOX5. A small proportion of extranodal marginal zone lymphoma/mucosa-associated lymphoid tissue lymphoma or nodal marginal zone lymphoma cases were positive for ALOX5 (2/13 or 1/3, respectively). In contrast, no cases with diffuse large B-cell lymphoma, regardless of germinal center B cell (GCB) or non-GCB type, expressed ALOX5 (0/25 cases). These findings suggest that ALOX5 may be a novel marker for identifying the cell of origin of B-cell lymphoma. Further investigation is required to clarify the biological significance of ALOX5 expression in lymphoma cells.
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  • 文章类型: Journal Article
    BACKGROUND: ALOX5, IL6R and SFTPD are all immune related genes that may be involved in the development of lung cancer. We sought to explore the effect of polymorphisms of these genes on the risk of lung cancer.
    METHODS: Six single nucleotide polymorphisms (SNPs) were genotyped using a MassARRAY platform in a case-control cohort including 550 patients with lung cancer and 550 healthy controls.
    RESULTS: The rs4845626-T and rs4329505-C alleles were associated with a decreased risk of lung cancer (p < 0.001), while the rs745986-G and rs2245121-A alleles were correlated with an increased risk of lung cancer (p < 0.01). The rs4845626-GT/GG and rs4329505-TC genotypes were protective against lung cancer (p < 0.001). However, the rs745986-AG and rs2245121-AG/AA genotypes were associated with an increased risk of lung cancer (p < 0.01). Stratification analysis showed that the rs4845626 and rs4329505 polymorphisms of IL6R were associated with a reduced risk of lung cancer in both smokers and nonsmokers (p < 0.05). However, rs892690, rs745986 and rs2115819 of ALOX5 were associated with an increased risk of disease in nonsmokers, while rs2245121 of SFTPD was correlated with a higher risk of disease in smokers (p < 0.05).
    CONCLUSIONS: Our results provide candidate SNPs for early screening for lung cancer and new clues for further study of the pathogenesis of the disease.
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