title: Gene expression of Toll-like receptor-2, Toll-like receptor-4, and MD2 is differentially regulated in rabbits with Escherichia coli pneumonia.
abstract: Sepsis, a common sequela to Gram-negative pneumonia, results in considerable morbidity and mortality in hospitalized patients. The goal of this study was to determine whether Gram-negative pneumonia alters the expression TLR2, TLR4, and MD2 in lungs or in organs distant to the site of the primary infection. The cDNA sequence coding open reading frames for rabbit TLR2, TLR4, and MD2 were cloned and expressed in Escherichia coli, and specific polyclonal antibodies and polymerase chain reaction (PCR) probes were produced to identify changes in these receptors in rabbits with Gram-negative pneumonia. Using tissues from lungs and distant organs, we show that TLR2, TLR4, and MD2 gene expression is differentially regulated in rabbits with E. coli pneumonia. The increased expression of TLR2 and TLR4 could play an important role in the innate immune response to bacterial infection in the lungs, and improve pathogen recognition and bacterial clearance. In contrast, the increased gene expression of TLR2, TLR4, and MD2 in organs distant to the primary site of infection may contribute to the deleterious systemic inflammatory response observed in patients with sepsis.
authors.affiliation: Pulmonary Research Laboratories at the Seattle Department of Veterans Affairs Medical Center, University of Washington School of Medicine, 151L 1660 South Columbian Way, Seattle, WA 98108, USA.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kajikawa
authors.forename: Charles W
authors.initials: CW
authors.lastname: Frevert
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Lin
authors.forename: Richard B
authors.initials: RB
authors.lastname: Goodman
authors.forename: Steve M
authors.initials: SM
authors.lastname: Mongovin
authors.forename: Venus
authors.initials: V
authors.lastname: Wong
authors.forename: Kim
authors.initials: K
authors.lastname: Ballman
authors.forename: Bruno
authors.initials: B
authors.lastname: Daubeuf
authors.forename: Greg
authors.initials: G
authors.lastname: Elson
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Martin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004927:Escherichia coli Infections / Q000235:genetics*; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D018410:Pneumonia, Bacterial / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D000954:Antigens, Surface; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors