Lipopolysaccharide-induced inflammatory cytokine production by Schwann's cells dependent upon TLR4 expression.
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.
Hao
Hsiao-Nan
HN
Department of Orthopaedic Surgery, Wayne State University, Detroit, MI 48823, United States. ab0770@wayne.edu
Peduzzi-Nelson
Jean D
JD
VandeVord
Pamela J
PJ
Barami
Kaveh
K
DeSilva
Stephen P
SP
Pelinkovic
Dalip
D
Morawa
Lawrence G
LG
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*
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