Polysaccharide isolated from Poria cocos sclerotium induces NF-kappaB/Rel activation and iNOS expression through the activation of p38 kinase in murine macrophages.
In our previous studies, we showed that PCSC, a polysaccharide isolated from Poria cocos, activated macrophages to induce the translocation of NF-kappaB/Rel into nucleus and DNA binding to its cognate site in the promoter of iNOS gene [Int. Immunopharmacol. 3 (2003) 1353]. In the present study, we investigated the role of p38 kinase pathway and membrane receptors (CD14, Toll-like receptor 4 (TLR4), and CR3) in mediating nitric oxide (NO) production and NF-kappaB/Rel activation induced by PCSC. Treament of RAW 264.7 cells with PCSC resulted in significant activation of p38. The specific p38 inhibitor SB203580 abrogated the PCSC-induced NF-kappaB/Rel activation and NO generation, whereas the selective mitogen-activated protein kinase/extracellular signal-regulated kinase 1 (MEK-1) inhibitor PD98059 did not affect the NF-kappaB/Rel and NO induction. Treatment of RAW 264.7 cells with anti-CD14 Ab, anti-TLR4 Ab, and anti-CR3 Absignificantly blocked PCSC-induced NO production activation. In conclusion, we demonstrate that PCSC induces NF-kappaB/Rel activation and iNOS expression through the CD14, TLR4, and CR3 membrane receptor and p38 kinase which is critically involved in the signal transduction leading to NF-kappaB/Rel activation in murine macrophages.
Lee
Kun Yeong
KY
Department of Pharmacology, Chosun University College of Medicine, 375 Susukdong, Kwangju 501-709, South Korea.
You
Ho Jin
HJ
Jeong
Hye Gwang
HG
Kang
Jong Soon
JS
Kim
Hwan Mook
HM
Rhee
Sang Dal
SD
Jeon
Young Jin
YJ
D000818:Animals; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D020572:Oncogene Proteins v-rel / Q000096:biosynthesis*; D020072:Polyporales; D011134:Polysaccharides / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D018950:Lipopolysaccharide Receptors; D016177:Macrophage-1 Antigen; D016328:NF-kappa B; D009573:Nitrites; D020572:Oncogene Proteins v-rel; D011134:Polysaccharides; D011971:Receptors, Immunologic; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases