title: Extracellular Release of CD11b by TLR9 Stimulation in Macrophages.
abstract: CpG-DNA upregulates the expression of pro-inflammatory cytokines, chemokines and cell surface markers. Investigators have shown that CD11b (integrin αM) regulates TLR-triggered inflammatory responses in the macrophages and dendritic cells. Therefore, we aimed to identify the effects of CpG-DNA on the expression of CD11b in macrophages. There was no significant change in surface expression of CD11b after CpG-DNA stimulation. However, CD11b was released into culture supernatants after stimulation with phosphorothioate-backbone modified CpG-DNA such as PS-ODN CpG-DNA 1826(S). In contrast, MB-ODN 4531 and non-CpG-DNA control (regardless of backbone type and liposome-encapsulation) failed to induce release of CD11b. Therefore, the context of the CpG-DNA sequence and phosphorothioate backbone modification may regulate the effects of CpG-DNA on CD11b release. Based on inhibitor studies, CD11b release is mediated by p38 MAP kinase activation, but not by the PI3K and NF-κB activation. CD11b release is mediated by lysosomal degradation and by vacuolar acidification in response to CpG-DNA stimulation. The amount of CD11b in the exosome precipitant was significantly increased by CpG-DNA stimulation in vivo and in vitro depending on TLR9. Our observations perhaps give more insight into understanding of the mechanisms involved in CpG-DNA-induced immunomodulation in the innate immunity.
authors.affiliation: Center for Medical Science Research, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Dongbum
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Te Ha
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Center for Medical Science Research, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Guang
authors.initials: G
authors.lastname: Wu
authors.affiliation: Center for Medical Science Research, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Byoung Kwon
authors.initials: BK
authors.lastname: Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Ha
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Yong-Sung
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, College of Natural Science, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Keunwook
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Younghee
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Center for Medical Science Research, Hallym University College of Medicine, Chuncheon, Republic of Korea.|Department of Microbiology, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Hyung-Joo
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism*; D002460:Cell Line; D055354:Exosomes / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D039481:CD11b Antigen; D009838:Oligodeoxyribonucleotides; D047428:Protein Kinase Inhibitors; D051217:Toll-Like Receptor 9; D048051:p38 Mitogen-Activated Protein Kinases