Activation of macrophages by polysaccharide isolated from Paecilomyces cicadae through toll-like receptor 4

• Published in: Food and chemical toxicology Vol. 50; no. 9; pp. 3190 - 3197
• Main Authors: Kim, Hyung Sook, Kim, Yeon Jin, Lee, Hong Kyung, Ryu, Hwa Sun, Kim, Ji Sung, Yoon, Mi Jung, Kang, Jong Soon, Hong, Jin Tae, Kim, Youngsoo, Han, Sang-Bae
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.2012; Elsevier
• Subjects: Animals; Base Sequence; Biological and medical sciences; Cell Line; Cytokines - genetics; DNA Primers; gene expression; immunomodulators; interleukin-1beta; interleukin-6; Macrophage; Macrophage Activation - drug effects; macrophages; MAP Kinase Signaling System; MAPK; Medical sciences; Mice; Mice, Inbred C3H; mitogen-activated protein kinase; NF-kappa B - metabolism; NF-κB; nitric oxide; Nitric Oxide - biosynthesis; Paecilomyces; Paecilomyces - chemistry; Paecilomyces cicadae; phosphorylation; Polysaccharide; Polysaccharides - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; signal transduction; TLR4; Toll-like receptor 4; Toll-Like Receptor 4 - metabolism; Toxicology; transcription factor NF-kappa B; tumor necrosis factor-alpha; NO; PMB; CR3; JNK; PRRs; SEAP; siRNA; MAPK; LPS; IκB; NF-κB; Paecilomyces cicadae; TLR; PCP; Polysaccharide; TLR4; BM-Mac; ERK; Macrophage; B; Toll like receptor 4; Enzyme; Biochemical compound; Transferases; Mitogen-activated protein kinase; Oside; Fungi; Signal transduction; Paecilomyces; NF; Isolation; Carbohydrate; Mould; Fungi Imperfecti; Microorganism; Transcription factor NFκB
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2012.05.051

► PCP isolated from Paecilomyces cicadae increases NO production and cytokine gene expression in macrophages. ► PCP activates macrophages through TLR4 membrane receptor. ► PCP activates MAPKs and NF-κB signaling downstream from TLR4. ► NF-κB and p38 play a crucial role in PCP-induced NO production by macrophages. Paecilomyces cicadae have been reported to have immunomodulatory properties. In this study, we investigated the effect of polysaccharide (PCP) isolated from P. cicadae on the macrophages. PCP increased the production of nitric oxide (NO) and the gene expression of IL-1β, IL-6, and TNF-α in RAW 264.7 cells. To investigate the membrane receptor, we examined the effect of PCP on primary macrophages isolated from wild type C3H/HeN and C3H/HeJ mice having mutant-TLR4. PCP induced NO production and cytokine gene expression in macrophages from C3H/HeN, but not from tlr4-mutated C3H/HeJ mice, which suggests that TLR4 is the membrane receptor for PCP. PCP induced the phosphorylation of ERK, JNK, and p38, and the nuclear translocation of NF-κB p50/p65, which are the main signaling molecules downstream from TLR4. Among them, p38 and NF-κB signaling played a crucial role in PCP-induced NO production by macrophages. These results indicate that PCP activates macrophages through the TLR4 signaling pathway.