PMID- 31766621 OWN - NLM STAT- MEDLINE DCOM- 20200406 LR - 20200408 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 24 IP - 23 DP - 2019 Nov 22 TI - Curdlan (Alcaligenes faecalis) (1-->3)-beta-d-Glucan Oligosaccharides Drive M1 Phenotype Polarization in Murine Bone Marrow-Derived Macrophages via Activation of MAPKs and NF-kappaB Pathways. LID - 10.3390/molecules24234251 [doi] LID - 4251 AB - Functional oligosaccharides, particularly curdlan (1-->3)-beta-d-glucan oligosaccharides (GOS), play important roles in modulating host immune responses. However, the molecular mechanisms underlying the immunostimulatory effects of GOS on macrophage polarization are not clear. In this work, GOS (5-1000 microg/mL) were non-toxic to bone marrow-derived macrophages (BMDMs) with improved pinocytic and bactericidal capacities. Incubation with GOS (100 microg/mL) induced M1 phenotype polarization of BMDMs as evidenced by increased CD11c(+)/CD86(+) (10.1%) and M1 gene expression of inducible nitric oxide synthase, interleukin (IL)-1beta, and chemokine C-C-motif ligand 2. Accordingly, the secretion of cytokines IL-1beta, IL-6, monocyte chemotactic protein-1, and tumor necrosis factor-alpha, as well as the nitrite release of BMDMs were increased by GOS (100 microg/mL). Expression of mitogen-activated protein kinases (MAPKs) of phosphorylated (p)-c-Jun amino-terminal kinase, p-extracellular signal regulated kinase, and p-p38 in BMDMs were increased by GOS, as well as the p-Stat1. Moreover, nuclear factor-kappa B (NF-kappaB) p-p65 expression in BMDMs was promoted by GOS while it suppressed IkappaBalpha expression. Receptor blocking with anti-CR3 (CD11b/CD18) and anti-toll-like receptor (TLR) 2 antibodies diminished GOS induced M1 phenotype polarization with reduced mRNA expression of M1 genes, decreased cytokine and nitrite releases, and suppressed signaling pathway activation. Thus, CR3 (CD11b/CD18) and TLR2 mediated activation of MAPKs and NF-kappaB pathways are responsible for GOS induced polarization of BMDMs. FAU - Liu, Jun AU - Liu J AD - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. AD - Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China. AD - Key Laboratory of Food Bioengineering (China National Light Industry), College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Qinghua Donglu, Haidian District, Beijing 100083, China. FAU - Tang, Jiqing AU - Tang J AD - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. FAU - Li, Xiuting AU - Li X AUID- ORCID: 0000-0002-3364-8191 AD - Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China. FAU - Yan, Qiaojuan AU - Yan Q AD - Bioresource Utilization Laboratory, College of Engineering, China Agricultural University, Beijing 100083, China. FAU - Ma, Junwen AU - Ma J AD - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. FAU - Jiang, Zhengqiang AU - Jiang Z AD - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. AD - Key Laboratory of Food Bioengineering (China National Light Industry), College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Qinghua Donglu, Haidian District, Beijing 100083, China. LA - eng GR - 31630096/National Natural Science Foundation of China/ GR - 2017YFD0400204/The National Key Research and Development Program of China/ PT - Journal Article DEP - 20191122 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 0 (Oligosaccharides) RN - 0 (beta-Glucans) RN - 6930DL209R (curdlan) SB - IM MH - Alcaligenes faecalis MH - Animals MH - Cell Polarity/drug effects MH - Cell Proliferation MH - Cells, Cultured MH - Cytokines/genetics MH - Gene Expression Regulation/drug effects MH - MAP Kinase Signaling System/*drug effects MH - Macrophage Activation MH - Macrophages/*cytology/drug effects/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/*metabolism MH - Oligosaccharides/chemical synthesis/chemistry/*pharmacology MH - Phosphorylation MH - Pinocytosis/drug effects MH - Salmonella typhimurium/drug effects MH - beta-Glucans/*chemistry/pharmacology PMC - PMC6930549 OTO - NOTNLM OT - curdlan (1-->3)-beta-d-glucan oligosaccharides OT - macrophage polarization OT - mitogen-activated protein kinases OT - nuclear factor-kappa B OT - receptor blocking COIS- The authors declare no conflicts of interest. EDAT- 2019/11/27 06:00 MHDA- 2020/04/09 06:00 PMCR- 2019/11/22 CRDT- 2019/11/27 06:00 PHST- 2019/10/23 00:00 [received] PHST- 2019/11/15 00:00 [revised] PHST- 2019/11/20 00:00 [accepted] PHST- 2019/11/27 06:00 [entrez] PHST- 2019/11/27 06:00 [pubmed] PHST- 2020/04/09 06:00 [medline] PHST- 2019/11/22 00:00 [pmc-release] AID - molecules24234251 [pii] AID - molecules-24-04251 [pii] AID - 10.3390/molecules24234251 [doi] PST - epublish SO - Molecules. 2019 Nov 22;24(23):4251. doi: 10.3390/molecules24234251.