Safflower polysaccharides activate the transcription factor NF-κB via Toll-like receptor 4 and induce cytokine production by macrophages

• Published in: International immunopharmacology Vol. 2; no. 8; pp. 1155 - 1162
• Main Authors: Ando, Izuru, Tsukumo, Yoshinori, Wakabayashi, Tetsuya, Akashi, Sachiko, Miyake, Kensuke, Kataoka, Takao, Nagai, Kazuo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2002
• Subjects: Animals; Carthamus tinctorius; Cell Line; Cytokine production; Cytokines - biosynthesis; Dose-Response Relationship, Drug; Drosophila Proteins; Female; Humans; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Mice; Mice, Inbred C3H; NF-kappa B - metabolism; NF-κB; Plant Components, Aerial; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Polysaccharides; Polysaccharides - pharmacology; Receptors, Cell Surface - genetics; Receptors, Cell Surface - physiology; Safflower; TLR4; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptors; Trans-Activators - pharmacology; NF-κB; Safflower; Polysaccharides; TG; Cytokine production; PGN; LTA; TLR; TIR; TLR4; LPS; PEC
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/S1567-5769(02)00076-0

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 IκBα essential for the activation of the transcription factor NF-κB. 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-α 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-κB signaling pathway via TLR4.