title: Lipopolysaccharide-induced inflammatory cytokine production by Schwann's cells dependent upon TLR4 expression.
abstract: Signaling of Toll-like receptor-4 (TLR4) through its cognate ligand endotoxin appears critical in tissue inflammation associated with bacterial infection. We found that anti-GM1 antibody (Ab) enhances TLR4 expression in Schwann's cells (SCs) in vivo and in vitro. The anti-GM1 Ab-treated SC also showed increased release of pro-inflammation cytokines IL-1beta and TNF-alpha after incubation with lipopolysaccharide (LPS). Furthermore, down-regulation of TLR4 expression using antisense oligonucleotides targeted to TLR4 mRNA suppressed cytokine production in LPS stimulated cultures. These findings suggest that elevation of TLR4 expression increases sensitivity of SC to LPS and production of inflammatory mediators that may be responsible for peripheral nerve dysfunction.
authors.affiliation: Department of Orthopaedic Surgery, Wayne State University, Detroit, MI 48823, United States. ab0770@wayne.edu
authors.forename: Hsiao-Nan
authors.initials: HN
authors.lastname: Hao
authors.forename: Jean D
authors.initials: JD
authors.lastname: Peduzzi-Nelson
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: VandeVord
authors.forename: Kaveh
authors.initials: K
authors.lastname: Barami
authors.forename: Stephen P
authors.initials: SP
authors.lastname: DeSilva
authors.forename: Dalip
authors.initials: D
authors.lastname: Pelinkovic
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Morawa
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4