title: CD14 expression in the first 24h of sepsis: effect of -260C>T CD14 SNP.
abstract: 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.
authors.affiliation: Faculdade de Biociências and Hospital São Lucas (HSL), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil.
authors.forename: Bibiana Butkus
authors.initials: BB
authors.lastname: de Aguiar
authors.forename: Ingrid
authors.initials: I
authors.lastname: Girardi
authors.forename: Diego D'Avila
authors.initials: DD
authors.lastname: Paskulin
authors.forename: Everaldo
authors.initials: E
authors.lastname: de Franca
authors.forename: Cláudia
authors.initials: C
authors.lastname: Dornelles
authors.forename: Fernando Suparregui
authors.initials: FS
authors.lastname: Dias
authors.forename: Cristina
authors.initials: C
authors.lastname: Bonorino
authors.forename: Clarice Sampaio
authors.initials: CS
authors.lastname: Alho
mesh_terms: 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
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors