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紫外线B诱导的人类皮肤接触敏感性诱导抑制与肿瘤坏死因子-α -308或白细胞介素-10基因多态性无关。

Ultraviolet B induced suppression of induction of contact sensitivity in human skin is not associated with tumour necrosis factor-alpha-308 or interleukin-10 genetic polymorphisms.

作者信息

Allen M H, Skov L, Barber R, Trembath R, Simon J, Baadsgaard O, Barker J N

机构信息

St John's Institute of Dermatology, St Thomas' Hospital, London, SE1 7EH, U.K.

出版信息

Br J Dermatol. 1998 Aug;139(2):225-9. doi: 10.1046/j.1365-2133.1998.02358.x.

Abstract

Low doses of ultraviolet B (UVB) can induce localized immunosuppression in skin. This effect may be important in the induction of skin cancers and is thought to be mediated by tumour necrosis factor (TNF) alpha and interleukin (IL) 10 in conjunction with other factors. In humans a transition polymorphism in the TNF-alpha gene may affect TNF-alpha secretion and the promoter region of the IL-10 gene contains a CA repeat polymorphism which may affect gene function. We have therefore investigated the association of these polymorphisms with UVB-induced immunosuppression in humans. Volunteers (n = 42) were irradiated with UVB then sensitized on irradiated skin with diphenylcyclopropanone (DPCP) and subsequently antigen challenged with DPCP. DNA was extracted from blood samples and volunteers genotyped for the TNF-alpha polymorphism by polymerase chain reaction (PCR) and restriction digestion. The CA repeat polymorphism was amplified by PCR and sized by gel electrophoresis. Twenty-four volunteers were susceptible to UVB-induced immunosuppression and 18 were resistant. The association of allele frequencies and phenotype was statistically tested using a chi2-test. For both the TNF-alpha and IL-10 polymorphisms, there was no statistically significant association between allele types and response to UVB. These results indicate that variation in the immune response to UVB in humans is not associated with the TNF-alpha-308 transition or IL-10 CA repeat polymorphisms, although other as yet undetected DNA sequence variants of these genes may be involved.

摘要

低剂量的紫外线B(UVB)可诱导皮肤局部免疫抑制。这种效应在皮肤癌的诱发中可能很重要,并且被认为是由肿瘤坏死因子(TNF)α和白细胞介素(IL)10与其他因素共同介导的。在人类中,TNF-α基因的一个转换多态性可能会影响TNF-α的分泌,而IL-10基因的启动子区域含有一个CA重复多态性,这可能会影响基因功能。因此,我们研究了这些多态性与人类UVB诱导的免疫抑制之间的关联。志愿者(n = 42)接受UVB照射,然后在照射过的皮肤上用二苯基环丙烷酮(DPCP)致敏,随后用DPCP进行抗原激发。从血样中提取DNA,通过聚合酶链反应(PCR)和限制性酶切对志愿者进行TNF-α多态性基因分型。通过PCR扩增CA重复多态性,并通过凝胶电泳确定其大小。24名志愿者对UVB诱导的免疫抑制敏感,18名志愿者具有抗性。使用卡方检验对等位基因频率与表型之间的关联进行统计学检验。对于TNF-α和IL-10多态性,等位基因类型与对UVB的反应之间均无统计学上的显著关联。这些结果表明,人类对UVB免疫反应的差异与TNF-α -308转换或IL-10 CA重复多态性无关,尽管这些基因的其他尚未检测到的DNA序列变异可能参与其中。

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