Molecular medicine (Cambridge, Mass.) · 2024
Molecular profiles of blood from numerous species that differ in sensitivity to acute inflammation.
СтатьяПоддержка NIH: внешняя программаПоддержка правительства СШАНазвание и аннотация: Перевод в очереди
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Gregory David J, Han Feifei, Li Peng, Gritsenko Marina A, Kyle Jennifer, Riley Frank E, Chavez Deborah, Yotova Vania, Sindeaux Renata H M, Hawash Mohamed B F, Xu Fengyun, Hung Li-Yuan, Hayden Douglas L, Tompkins Ronald G, Lanford Robert E, Kobzik Lester, Hellman Judith, Jacobs Jon M, Barreiro Luis B, Xiao Wenzhong, Warren H Shaw
Аннотация
Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species. After LPS stimulation, maximally different genes in resilient species included genes that detoxify LPS, diminish bacterial growth, discriminate sepsis from SIRS, and play roles in autophagy and apoptosis. The findings reveal the molecular landscape of species differences in inflammation. This may inform better selection of species for pre-clinical models and could lead to new therapeutic strategies that mimic mechanisms in inflammation-resilient species to limit inflammation without causing immunosuppression.