title: Retinol suppresses the activation of Toll-like receptors in MyD88- and STAT1-independent manners.
abstract: Dysregulation of Toll-like receptor (TLR) activation is well known to be linked to development and aggravation of inflammatory diseases and immune disorders. Retinol is reported to participate in regulation of immune responses. However, it has not been fully understood how retinol regulates TLR activation in macrophages. Our results showed that retinol suppressed the expression of various inflammatory cytokines in bone marrow-derived macrophages stimulated with ligands of TLR2, TLR3, or TLR4. These demonstrate that inhibitory effect of retinol is not limited to a single TLR. Inhibitory effect of retinol on lipopolysaccharide-induced target gene expression was still observed in myeloid differentiation primary-response protein 88 (MyD88)- or signal transducer and activator of transcription 1 (STAT1)-deficient macrophages, indicating that MyD88 and STAT1 are dispensable for retinol-mediated blockade of TLRs. Together, the results demonstrate that retinol suppresses the activation of TLRs in macrophages resulting in downregulation of inflammatory gene expression and further suggest that beneficial effect of retinol is mediated through regulation of TLR-mediated inflammatory responses.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Koo
authors.forename: Mi-Ryoung
authors.initials: MR
authors.lastname: Song
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D015870:Gene Expression; D007249:Inflammation; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors; D051196:Toll-Like Receptor 3 / Q000037:antagonists & inhibitors; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014801:Vitamin A / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology
chemical_list: D007376:Interleukin-2; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; C519703:TLR3 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D014801:Vitamin A; D015847:Interleukin-4; D007371:Interferon-gamma