Activation of macrophages by polysaccharide isolated from Paecilomyces cicadae through toll-like receptor 4.
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.
College of Pharmacy and Medical Research Center (CICT), Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
Hyung Sook
HS
Kim
Yeon Jin
YJ
Kim
Hong Kyung
HK
Lee
Hwa Sun
HS
Ryu
Ji Sung
JS
Kim
Mi Jung
MJ
Yoon
Jong Soon
JS
Kang
Jin Tae
JT
Hong
Youngsoo
Y
Kim
Sang-Bae
SB
Han
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers; D020935:MAP Kinase Signaling System; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010143:Paecilomyces / Q000737:chemistry*; D011134:Polysaccharides / Q000494:pharmacology*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D016207:Cytokines; D017931:DNA Primers; D016328:NF-kappa B; D011134:Polysaccharides; D034741:RNA, Small Interfering; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide