title: Safflower polysaccharides activate the transcription factor NF-kappa B via Toll-like receptor 4 and induce cytokine production by macrophages.
abstract: Two active polysaccharide fractions (SF1 and SF2) purified from dried safflower petals (Carthamus tinctorius L.) stimulated the synthesis of various cytokines by peritoneal macrophages. In a number of cell types, SF1 and SF2 induced a rapid degradation of IkappaB alpha essential for the activation of the transcription factor NF-kappaB. Toll-like receptor 4 (TLR4), but not TLR2, was expressed in all cell lines that responded to SF1 and SF2. Enforced expression of TLR4 and MD-2 rendered responsiveness to SF1 and SF2. Moreover, these safflower polysaccharides failed to induce the production of TNF-alpha and NO by peritoneal macrophages prepared from C3H/HeJ mice that have a point mutation in the Tlr4 gene. Thus, these observations clearly indicate that safflower polysaccharides activate the NF-kappaB signaling pathway via TLR4.
mesh_terms: D000818:Animals; D031187:Carthamus tinctorius; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins; D005260:Female; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000378:metabolism*; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015534:Trans-Activators / Q000494:pharmacology
chemical_list: D016207:Cytokines; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010936:Plant Extracts; D011134:Polysaccharides; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015534:Trans-Activators