title: Toll-like receptor 1/2 stimulation induces elevated interleukin-8 secretion in polymorphonuclear leukocytes isolated from preterm and term newborn infants.
abstract: BACKGROUND
  Neonatal neutrophil dysfunction contributes to inflammatory tissue damage in newborn infants. Toll-like receptors (TLRs) activate the innate immune response through recognition of pathogen-associated molecular patterns. Expression and function of TLRs by neonatal neutrophils has not well been characterized.
  
  
  OBJECTIVE
  We hypothesized that, compared to polymorphonuclear leukocytes (PMNs) isolated from adults, neonatal PMNs isolated from either term or preterm infants express and release different levels of inflammatory cytokines and chemokines in response to stimulation with TLR1-9 agonists.
  
  
  METHODS
  We stimulated PMNs isolated from preterm (n = 12) and term (n = 10) infants as well as adults (n = 10) with agonists recognized by TLRs1-9 and quantified chemokine and cytokine expression and secretion by ELISA and Luminex® multiplex quantification assay.
  
  
  RESULTS
  Neonatal and adult PMNs stimulated with agonists recognized by TLRs1-9 differentially secrete inflammatory products. Signaling via TLR2 heterodimers is a potent mechanism for release of interleukin-8, a critical proinflammatory chemokine, by neonatal PMNs--a previously unrecognized facet of neonatal inflammation. Following TLR1/2 (PAM3CSK4) stimulation, interleukin-8 secretion by neonatal PMNs, whether term or preterm, substantially exceeds that of adult PMNs assayed in parallel.
  
  
  CONCLUSIONS
  These studies provide new insights relevant to the inflammatory biology of neonates, both term and preterm, and implicate exaggerated PMN recruitment in neonatal syndromes of dysregulated inflammation such as necrotizing enterocolitis or neonatal chronic lung disease.
authors.affiliation: Department of Pediatrics and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah 84108, USA.
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Thornton
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cody
authors.forename: Christian C
authors.initials: CC
authors.lastname: Yost
mesh_terms: D000328:Adult; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D016209:Interleukin-8 / Q000378:metabolism*; D055666:Lipopeptides / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051194:Toll-Like Receptor 1 / Q000819:agonists / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; C495342:TLR2 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2