Exopolysaccharide from Trichoderma pseudokoningii induces macrophage activation.
In this study, we evaluated the immunomodulatory activity of an exopolysaccharide (EPS) derived from Trichoderma pseudokoningii and investigated the molecular mechanism of EPS-mediated activation of macrophages. Results revealed that EPS could significantly induce the production of nitric oxide (NO), tumor necrosis factor (TNF)-α and interleukin (IL)-1β and enhance phagocytic activity in RAW 264.7 cells. Immunofluorescence staining indicated that EPS promoted the nuclear translocation of nuclear factor (NF)-κB p65 subunit. Western blot analysis showed that EPS increased the expression of inducible nitric oxide synthase (iNOS) protein, the degradation of IκB-α and the phosphorylation of mitogen-activated protein kinases (MAPKs). Furthermore, pretreatment of RAW 264.7 cells with specific inhibitors of NF-κB and MAPKs significantly attenuated EPS-induced TNF-α and IL-1β production. EPS also induced the inhibition of cytokine secretion by special antibodies against Toll-like receptor-4 (TLR4) and Dectin-1. These data suggest that EPS from Trichoderma pseudokoningii activates RAW 264.7 cells through NF-κB and MAPKs signaling pathways via TLR4 and Dectin-1.
Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Anhui Province Key Laboratory of Active Biological Macro-molecules, School of Pharmacy, Wannan Medical College, Wuhu 241002, China.
Guodong
G
Wang
Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Anhui Province Key Laboratory of Active Biological Macro-molecules, School of Pharmacy, Wannan Medical College, Wuhu 241002, China.
Lei
L
Zhu
Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Bo
B
Yu
Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Ke
K
Chen
Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Bo
B
Liu
Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Jun
J
Liu
Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Anhui Province Key Laboratory of Active Biological Macro-molecules, School of Pharmacy, Wannan Medical College, Wuhu 241002, China.
Guozheng
G
Qin
Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Anhui Province Key Laboratory of Active Biological Macro-molecules, School of Pharmacy, Wannan Medical College, Wuhu 241002, China.
Chunyan
C
Liu
Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: lhx900@aliyun.com.
Huixia
H
Liu
Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Anhui Province Key Laboratory of Active Biological Macro-molecules, School of Pharmacy, Wannan Medical College, Wuhu 241002, China; School of Life Science and National Glycoengineering Research Center, Shandong University, Jinan 250100, China. Electronic address: ksc313@126.com.
Kaoshan
K
Chen
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D062610:Fungal Polysaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007155:Immunologic Factors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D000067996:RAW 264.7 Cells; D014242:Trichoderma / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D062610:Fungal Polysaccharides; D007155:Immunologic Factors; D053583:Interleukin-1beta; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases
Dimethyl sulfoxide (PubChem CID: 679); Exopolysaccharide; Immunomodulation; Lipopolysaccharide (PubChem CID: 11970143); MAPKs; Macrophages; NF-κB; Nitric oxide (PubChem CID: 145068); Trichoderma pseudokoningii