EFFECTS OF CD14-159 C/T POLYMORPHISM ON CD14 EXPRESSION AND THE BALANCE BETWEEN PROINFLAMMATORY AND ANTI-INFLAMMATORY CYTOKINES IN WHOLE BLOOD CULTURE

Abstract

CD14 is an important receptor of innate immunity. When CD14 is anchored by ligands to LPS, peptidoglycans, or lipoteichoic acid, it can result in either proinflammatory or anti-inflammatory responses. To determine whether CD14-159 C/T polymorphism is associated with CD14 expression and the balance of proinflammatory and anti-inflammatory responses, we studied 118 healthy ethnic Han Chinese using a whole blood culture model. The CD14-159 C/T polymorphism was determined by polymerase chain reaction and subsequent HaeIII restriction enzyme digestion of the polymerase chain reaction products. Meanwhile, CD14 mRNA expression in leukocytes and the levels of soluble CD14, TNF-alpha, IL-6, and IL-10 were also determined in the supernatants. Among the 118 individuals, there were 40 TT homozygotes, 62 heterozygotes, and 16 subjects homozygous for C allele. After LPS stimulation, the levels of CD14 mRNA expression in TT and TC genotypes were significantly higher than in CC homozygotes (P = 0.017), and soluble CD14 levels were also higher than in CC genotypes (P = 0.008). In addition, TT homozygotes had the highest LPS-stimulated TNF-alpha, IL-6 production (P = 0.044, P = 0.004), and the lowest IL-10 release (P = 0.003). In conclusion, CD14-159 C/T polymorphism is correlated with CD14 expression and may thus influence the balance of proinflammatory and anti-inflammatory responses in ethnic Han Chinese. These results suggest that CD14-159 C/T polymorphism might partly explain the difference in predisposition to develop complications of infectious diseases in different patients and may provide a therapeutic target for sepsis intervention strategies.