CD14 expression in the first 24h of sepsis: effect of -260C>T CD14 SNP.
Sepsis is defined as systemic inflammation caused by infection. The membrane bound CD14 (mCD14) or the soluble form (sCD14) play a crucial role facing Gram-negative and Gram-positive sepsis since they are pattern recognition receptors of the innate immune response enabling cells to produce inflammatory cytokines against bacterial infections. A -260C>T single nucleotide polymorphism (SNP) was detected in the promoter modulating the CD14 gene expression. We hypothesized that the CD14 expression depends of the genetic inheritance of -260C>T CD14 SNP and it is modulated by sepsis condition. We investigated human CD14 expression on early sepsis diagnosis (in vivo) and after LPS stimulation (in vitro), and determined the -260C>T CD14 SNP. We found that TT homozygotes showed higher mCD14 density (p = 0.0207), but not different sCD14 levels when compared to the CT+CC genotypes. Monocyte mCD14 density and sCD14 serum levels in our sample of early 14 septic patients were significantly higher than normal 30 controls (p<0.0001). Our results suggest that the -260TT CD14 genotype is associated with higher monocyte mCD14, but not sCD14 expression, and that in the first 24 h after sepsis diagnosis, both monocyte mCD14 density and sCD14 levels are elevated, similarly to what is observed in vitro upon challenge with LPS.
de Aguiar
Bibiana Butkus
BB
Faculdade de Biociências and Hospital São Lucas (HSL), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil.
Girardi
Ingrid
I
Paskulin
Diego D'Avila
DD
de Franca
Everaldo
E
Dornelles
Cláudia
C
Dias
Fernando Suparregui
FS
Bonorino
Cristina
C
Alho
Clarice Sampaio
CS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D016019:Survival Analysis; D013997:Time Factors
D016207:Cytokines; D018950:Lipopolysaccharide Receptors