title: Involvement of CD14 and toll-like receptor 4 in the acute phase response of serum amyloid A proteins and serum amyloid P component in the liver after burn injury.
abstract: Acute phase proteins such as serum amyloid A proteins (SAAs) and serum amyloid P component (SAP) are induced in the liver after various insults (e.g., infection, injury). The cellular and molecular mechanisms controlling the expression of these acute phase proteins may be specifically designed for different insults. The roles of two central molecules of the lipopolysaccharide (LPS)-mediated inflammation pathway (CD14 and toll-like receptor 4 [Tlr4]) were investigated for the regulation of SAAs and SAP in the liver of mice after an 18% total body surface area burn injury. RT-PCR analysis revealed a subtype- and time-dependent induction of SAA mRNAs between 3 h and 3 days, while there was a peak induction of SAP mRNA at day 1. Marked elevations of SAA and SAP protein levels at day 1 supported the mRNA data. Furthermore, a differential regulation of SAAs and SAP mRNAs was noted between CD14 knockout (KO) and their control mice after injury. SAA protein was induced to a lesser degree after injury in C3H/HeJ (Tlr4-defective) mice than in their control mice. In addition, in both CD14 KO and C3H/HeJ mice, the induction of SAP protein was significantly reduced compared with respective controls. These data provide evidence that CD14 and Tlr4 participate, at least in part, in a cascade of signaling events that control the immediate-early and differential induction of SAAs and SAP in the liver after injury. They also suggest that LPS may be one of the initial inducing agents associated with these acute phase responses in the liver after injury.
authors.affiliation: Burn Research, Shriners Hospitals for Children Northern California, Department of Surgery, University of California at Davis, Sacramento 95817, USA.
authors.forename: Kiho
authors.initials: K
authors.lastname: Cho
authors.forename: Tam N
authors.initials: TN
authors.lastname: Pham
authors.forename: Sicily D
authors.initials: SD
authors.lastname: Crivello
authors.forename: Jayoung
authors.initials: J
authors.lastname: Jeong
authors.forename: Tajia L
authors.initials: TL
authors.lastname: Green
authors.forename: David G
authors.initials: DG
authors.lastname: Greenhalgh
mesh_terms: D000210:Acute-Phase Reaction; D000818:Animals; D015153:Blotting, Western; D002056:Burns; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000502:physiology*; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000096:biosynthesis*; D000683:Serum Amyloid P-Component / Q000096:biosynthesis*; D013997:Time Factors; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000685:Serum Amyloid A Protein; D000683:Serum Amyloid P-Component; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors