Role of MyD88 in TLR agonist-induced functional alterations of human adipose tissue-derived mesenchymal stem cells.
Toll-like receptors (TLRs) sense microorganism components and are critical host mediators of inflammation during infection. Recently, TLRs have been reported to be involved in cell proliferation and differentiation. We previously reported that TLR agonists might affect proliferation and differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs). In this study, we sought to determine whether TLR signaling is dependent on MyD88 in hASCs. The hASCs were downregulated using LV-GFP-miR-MyD88, a lentiviral construct inserted siRNA against human MyD88 that significantly inhibited cell proliferation. MyD88 downregulation reduced NF-kappaB activation and enhancement of osteogenic differentiation induced by peptidoglycan (PGN) more significantly than that induced by lipopolysaccharide (LPS). Although LPS- and PGN-induced cytokine secretions were decreased greatly by MyD88 downregulation, IFN-gamma-induced protein-10 (IP10) and IFNbeta expression were enhanced by LPS irrespective of the downregulation of MyD88. These results suggest that TLR signaling is mediated via MyD88-independent pathways as well as MyD88-dependent pathways in hASCs and that MyD88 contributes to the regulation of cell proliferation and differentiation in hASCs.
Yu
Sungsook
S
BK21 Medical Science Education Center, Pusan National University, Pusan, 602-739, Korea. Sungsook@pusan.ac.kr
Cho
Hyun Hwa
HH
Joo
Hye Joon
HJ
Bae
Yong Chan
YC
Jung
Jin Sup
JS
D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology*; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010457:Peptidoglycan / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists*
D018925:Chemokines; C104577:IP10-Mig receptor; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D010457:Peptidoglycan; D034741:RNA, Small Interfering; D018121:Receptors, Cytokine; D051193:Toll-Like Receptors; D016899:Interferon-beta