PMID- 26093315 OWN - NLM STAT- MEDLINE DCOM- 20160517 LR - 20161125 IS - 1879-0003 (Electronic) IS - 0141-8130 (Linking) VI - 79 DP - 2015 Aug TI - Immunostimulatory polysaccharide isolated from the leaves of Diospyros kaki Thumb modulate macrophage via TLR2. PG - 971-82 LID - S0141-8130(15)00426-2 [pii] LID - 10.1016/j.ijbiomac.2015.06.023 [doi] AB - The objective of this study was to investigate the immunostimulatory effects of a polysaccharide fraction from the leaves of Diospyros kaki Thumb (PLE0) and the molecular mechanism responsible for its action in RAW 264.7 macrophages as well as in vivo effects on cyclophosphamide-induced immunosuppression in mice. PLE0 concentration-dependently activated the expressions of inducible nitric oxide synthase (iNOS) at the protein and mRNA levels and its promoter activity, and that these activations caused attendant increases the nitric oxide (NO) production. In addition, PLE0 increased the mRNA expressions of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6. Molecular data revealed that PLE0 increased the transcriptional activity and nuclear translocation of nuclear factor-kappaB (NF-kappaB) by inducing the degradation of inhibitory kappaBalpha (IkappaBalpha) and the phosphorylation of inhibitory kappaB kinase (IKK). Moreover, anti-toll-like receptor 2 (TLR2) antibody and myeloid differentiation primary response gene 88 (MyD88)-specific siRNA significantly reduce PLE0-induced NO production in RAW 264.7 macrophages. Pretreatment with PLE0 recovered cyclophosphamide-induced reductions in thymus and spleen indices as well as neutrophil counts. Taken together, our data suggest that PLE0 up-regulates the expressions of iNOS, TNF-alpha, IL-1beta, and IL-6 genes by activating TLR2-mediated NF-kappaB activations, and that these actions are responsible for its immunostimulatory effects. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Lee, Suel-Gie AU - Lee SG AD - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 130-710, Republic of Korea; Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-710, Republic of Korea. FAU - Jung, Ji-Yun AU - Jung JY AD - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 130-710, Republic of Korea; Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-710, Republic of Korea. FAU - Shin, Ji-Sun AU - Shin JS AD - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 130-710, Republic of Korea; Reactive Oxygen Species Medical Research Center, School of Medicine, Kyung Hee University, Seoul 130-710, Republic of Korea. FAU - Shin, Kwang-Soon AU - Shin KS AD - Department of Food Science and Biotechnology, Kyonggi University, Suwon, Gyeonggi-do 443-760, Republic of Korea. FAU - Cho, Chang-Won AU - Cho CW AD - Korea Food Research Institute, Seongnam, Gyeonggi-do 463-836, Republic of Korea. FAU - Rhee, Young-Kyoung AU - Rhee YK AD - Korea Food Research Institute, Seongnam, Gyeonggi-do 463-836, Republic of Korea. FAU - Hong, Hee-Do AU - Hong HD AD - Korea Food Research Institute, Seongnam, Gyeonggi-do 463-836, Republic of Korea. FAU - Lee, Kyung-Tae AU - Lee KT AD - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 130-710, Republic of Korea; Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-710, Republic of Korea. Electronic address: ktlee@khu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150617 PL - Netherlands TA - Int J Biol Macromol JT - International journal of biological macromolecules JID - 7909578 RN - 0 (I-kappa B Proteins) RN - 0 (Immunologic Factors) RN - 0 (Nfkbia protein, mouse) RN - 0 (Polysaccharides) RN - 0 (Tlr2 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Tumor Necrosis Factor-alpha) RN - 139874-52-5 (NF-KappaB Inhibitor alpha) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) SB - IM MH - Animals MH - Diospyros/chemistry MH - Gene Expression Regulation/drug effects MH - I-kappa B Proteins/biosynthesis MH - Immunologic Factors/genetics/*immunology/*isolation & purification/pharmacology MH - Macrophages/*drug effects/immunology MH - Mice MH - NF-KappaB Inhibitor alpha MH - Nitric Oxide Synthase Type II/biosynthesis MH - Plant Leaves/chemistry MH - Polysaccharides/genetics/*immunology/isolation & purification/pharmacology MH - Signal Transduction/drug effects MH - Toll-Like Receptor 2/biosynthesis/*genetics MH - Transcriptional Activation/drug effects MH - Tumor Necrosis Factor-alpha/biosynthesis OTO - NOTNLM OT - Immunostimulatory effects OT - Polysaccharide OT - Toll-like receptor 2 EDAT- 2015/06/21 06:00 MHDA- 2016/05/18 06:00 CRDT- 2015/06/21 06:00 PHST- 2015/04/20 00:00 [received] PHST- 2015/05/28 00:00 [revised] PHST- 2015/06/14 00:00 [accepted] PHST- 2015/06/21 06:00 [entrez] PHST- 2015/06/21 06:00 [pubmed] PHST- 2016/05/18 06:00 [medline] AID - S0141-8130(15)00426-2 [pii] AID - 10.1016/j.ijbiomac.2015.06.023 [doi] PST - ppublish SO - Int J Biol Macromol. 2015 Aug;79:971-82. doi: 10.1016/j.ijbiomac.2015.06.023. Epub 2015 Jun 17.