An integrated omics analysis: impact of microgravity on host response to lipopolysaccharide in vitro.

An integrated omics analysis: impact of microgravity on host response to lipopolysaccharide in vitro.
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DOI:
10.1186/1471-2164-15-659
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发表时间:
2014-08-07
期刊:
影响因子:
4.4
通讯作者:
Hammamieh R
Hammamieh R
中科院分区:
生物学2区
文献类型:
--
作者:
Chakraborty N;Gautam A;Muhie S;Miller SA;Jett M;Hammamieh R

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微重力通过增强病原体毒力和抑制宿主抵抗力来促进机会性感染。因此,外星感染可能会激活不同于陆地生物网络的潜在新型生物网络,而这只能通过以最小的地球偏见调查宿主与病原体的关系来探测。我们定制了一个细胞培养模块,将人内皮细胞暴露于脂多糖(LPS)。该测定是在 STS-135 航天飞机上进行的,同时进行的地面研究构成了基线。转录组学研究揭示了微重力中可能存在的免疫钝化抑制,尤其是 Lbp、MyD88 和 MD-2,它们编码负责早期 LPS 摄取的蛋白质。正如蛋白质组学研究表明的那样,某些细胞因子,例如 IL-6 和 IL-8,在微重力条件下对 LPS 损伤做出反应而激增。 B2M、TIMP-1 和 VEGR 的蛋白质组表达对比表明促生存适应和愈合机制受损。 miR-200a和miR-146b的差异表达表明太空飞行中的宿主对氧化应激的易感性,并进一步强调了微重力对免疫的影响。分子解释解释了微重力对宿主-病原体关系影响的病因,阐明了宿主细胞对脂多糖挑战的全面免疫钝化。较长时间的 LPS 暴露会导致宿主反应延迟,这可能无法有效防止病原体的机会性入侵。显着的后果包括随后无法募集生长因子和细胞凋亡减弱。有必要进行更大样本量的后续研究。本文的在线版本 (doi:10.1186/1471-2164-15-659) 包含补充材料,可供授权用户使用。
Microgravity facilitates the opportunistic infections by augmenting the pathogenic virulence and suppressing the host resistance. Hence the extraterrestrial infections may activate potentially novel bionetworks different from the terrestrial equivalent, which could only be probed by investigating the host-pathogen relationship with a minimum of terrestrial bias. We customized a cell culture module to expose human endothelial cells to lipopolysaccharide (LPS). The assay was carried out onboard the STS-135 spaceflight, and a concurrent ground study constituted the baseline. Transcriptomic investigation revealed a possible immune blunting in microgravity suppressing in particular Lbp, MyD88 and MD-2, which encode proteins responsible for early LPS uptake. Certain cytokines, such as IL-6 and IL-8, surged in response to LPS insult in microgravity, as suggested by the proteomics study. Contrasting proteomic expressions of B2M, TIMP-1 and VEGRs suggested impaired pro-survival adaptation and healing mechanisms. Differential expression of miR-200a and miR-146b suggested the susceptibility of hosts in spaceflight to oxidative stress and further underscored the influence of microgravity on the immunity. A molecular interpretation explaining the etiology of the microgravitational impact on the host-pathogen relationship elucidated comprehensive immune blunting of the host cells responding to LPS challenges. Longer LPS exposure prompted a delayed host response, potentially ineffectual in preventing pathogens from opportunistic invasion. Significant consequences include the subsequent failure in recruiting the growth factors and a debilitated apoptosis. Follow up studies with larger sample size are warranted. The online version of this article (doi:10.1186/1471-2164-15-659) contains supplementary material, which is available to authorized users.
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