Gene profiling in human blood leucocytes during recovery from septic shock
- 302 Downloads
To assess blood leucocytes gene profiling during recovery phase of septic shock; to test the relation between encoding gene expression and protein level.
Gene expression levels were studied at days 0, 1, 7 and 28 (D0, 1, 7 and 28) on a dedicated microarray of 340 genes involved in inflammatory processes.
16-bed intensive care unit, Lariboisière University hospital.
Seventeen septic shock patients enrolled when at least one additional organ dysfunction occurred.
Measurements and results
Changes over time were compared with D0 via the ratio Dx/D0. The time-related gene expression study showed significant changes in ten genes. Among them, S100A8 and S100A12 had a reduced expression over time compared with D0, whereas CD74's expression increased. The microarray results were validated by RT-qPCR for four genes. The S100A8 plasma levels decrease along recovery in parallel with the gene expression decrease. The CD74 gene expression evolution significantly correlated with HLA-DR monocyte expression.
These results are the first description of variations in expression of key inflammatory genes in the course of the septic shock recovery period.
KeywordsMicroarray Kinetic of gene expression CD 74 S100A gene and protein HLA-DR expression
This work was supported in part by “Programme Hospitalier Recherche Clinique (PHRC) AORO2006” and by “Quadrienal plan for research from the French Ministry of Research” EA 322.
- 6.Abraham E, Wunderink R, Silverman H, Perl TM, Nasraway S, Levy H, Bone R, Wenzel RP, Balk R, Allred RP et al. (1995) Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group. J Am Med Assoc 273:934–941CrossRefGoogle Scholar
- 7.Fisher CJ Jr, Dhainaut JF, Opal SM, Pribble JP, Balk RA, Slotman GJ, Iberti TJ, Rackow EC, Shapiro MJ, Greenman RL et al. (1994) Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. J Am Med Assoc 271:1836–1843CrossRefGoogle Scholar
- 9.Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV, Cho RJ, Chen RO, Brownstein BH, Cobb JP, Tschoeke SK, Miller-Graziano C, Moldawer LL, Mindrinos MN, Davis RW, Tompkins RG, Lowry SF (2005) A network-based analysis of systemic inflammation in humans. Nature 437:1032–1037PubMedCrossRefGoogle Scholar
- 22.Koike T, Harada N, Yoshida T, Morikawa M (1992) Regulation of myeloid-specific calcium binding protein synthesis by cytosolic protein kinase C. J Biochem (Tokyo) 112:624–630Google Scholar