title: Selective Toll--like receptor expression in human fetal lung.
abstract: Toll-like receptors (TLRs) are critical components of the innate immune system, acting as pattern recognition molecules and triggering an inflammatory response. TLR associated gene products are of interest in modulating inflammatory-related pulmonary diseases of the neonate. The ontogeny of TLR-related genes in human fetal lung has not been previously described and could elucidate additional functions and identify strategies for attenuating the effects of fetal inflammation. We examined the expression of 84 TLR-related genes on 23 human fetal lung samples from three groups with estimated ages of 60 (57-59 d), 90 (89-91 d), and 130 (117-154 d) d. By using a false detection rate algorithm, we identified 32 genes displaying developmental regulation with TLR2 having the greatest up-regulation of TLR genes (9.2-fold increase) and TLR4 unchanged. We confirmed the TLR2 up-regulation by examining an additional 133 fetal lung tissue samples with a fluorogenic polymerase chain reaction assay (TaqMan) and found an exponential best-fit curve during the study time. The best-fit curve predicts a 6.1-fold increase from 60 to 130 d. We conclude that TLR2 is developmentally expressed from the early pseudoglandular stage of lung development to the canalicular stage.
authors.affiliation: Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri 64108, USA. jepetrikin@cmh.edu
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Petrikin
authors.forename: Roger
authors.initials: R
authors.lastname: Gaedigk
authors.forename: J Steven
authors.initials: JS
authors.lastname: Leeder
authors.forename: William E
authors.initials: WE
authors.lastname: Truog
mesh_terms: D000465:Algorithms; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D008168:Lung / Q000196:embryology / Q000276:immunology*; D009024:Morphogenesis; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors