Disease relevance of Cd14

• Because endotoxin is a key activator of hepatic macrophages, this study was designed to test the hypothesis that LPS signaling through CD14 contributes to hepatic fibrosis caused by experimental cholestasis [1].
• Markers of liver fibrosis such as Sirius red staining, liver hydroxyproline, and alpha-smooth muscle actin expression were blunted in CD14(-/-) mice compared with wild-type mice after bile duct ligation [1].
• Survival of Vi-capsulated and Vi-deleted Salmonella typhi strains in cultured macrophage expressing different levels of CD14 antigen [2].

High impact information on Cd14

• The Heedless phenotype was positionally ascribed to a premature stop codon in Cd14 [3].
• Activation of STAT-3 and three STAT-3 responsive genes, Socs3, Cd14, and serum amyloid A2 were also blocked [4].
• To resolve this controversy and to establish a mouse model suitable for elucidation of the functions of human CD14 (hCD14) in vivo, we generated several lines of transgenic mice bearing different copy numbers of the hCd14 transgene on a murine Cd14(-/-) background [5].
• The macrophage activation by CAZ-released endotoxin as well as LPS was mainly dependent on the presence of serum factor and CD14 antigen [6].
• TNF-alpha induced a transient increase in levels of CD14 in plasma with a peak at 6 to 8 h, and this increase in levels of CD14 antigen in plasma was accompanied by increased levels of CD14 mRNA in lung, liver, and kidney [7].

Biological context of Cd14

• Serum levels of sCD14 in a founder with multiple copies of the transgene were several times higher than in transgenic animals with a single copy of Cd14 [5].
• In conclusion, these data demonstrate that endotoxin in a CD14-dependent manner exacerbates hepatic fibrogenesis and macrophage activation to produce oxidants and cytokines after bile duct ligation [1].
• Despite no difference in lymphocyte infiltration, the macrophage/monocyte activation marker OX42 (CD11b) and the oxidative stress/lipid peroxidation marker 4-hydroxynonenal were significantly upregulated in wild-type mice after bile duct ligation but not in CD14(-/-) mice [1].
• All possessed human chromosomes (mean number ranging from 4 to 14 depending on the clones studied), exhibited non-specific esterases (but no peroxidase activity) and expressed CD14 antigen and C3 receptors (but no MAX-1 antigen) [8].

Anatomical context of Cd14

• A mutant cell line, J7.DEF3, defective in expression of a CD14 antigen, responded equally well to taxol by producing TNF as did the parent J774.1 cells [9].
• Increased profibrogenic cytokine mRNA expression in the liver after bile duct ligation was significantly blunted in CD14(-/-) mice compared with the wild type [1].
• Both of these agents down-regulated CD45 (leukocyte common antigen) and monocyte-associated CD14 antigen on K-562 cells [10].

Other interactions of Cd14

• Because strain differences are known for Gbp1 and Pla2g2a, further analyses focused on Cd14 [11].
• Recombinant murine interleukin-1beta (IL-1beta) induced a transient increase in plasma levels of CD14 with a peak at 8 h, and this increase in plasma CD14 antigen was accompanied by increased levels of CD14 messenger ribonucleic acid (mRNA) in all organs examined [12].
• Studies utilizing a mutant cell line (J7.DEF3), which is defective in the expression of a CD14 antigen, showed that the increase in NO and iNOS mRNA caused by LTA is profoundly depressed in J7.DEF3 cells compared to that in parent J774 cells [13].

References