Role of MyD88 in TLR agonist-induced functional alterations of human adipose tissue-derived mesenchymal stem cells

• Published in: Molecular and cellular biochemistry 2008-10, Vol.317 (1-2), p.143-150
• Main Authors: Yu, Sungsook, Cho, Hyun Hwa, Joo, Hye Joon, Bae, Yong Chan, Jung, Jin Sup
• Format: Article
• Language: English
• Subjects: Adipogenesis - drug effects; Adipose tissue; Adipose Tissue - cytology; Biochemistry; Biomedical and Life Sciences; Body fat; Cardiology; Cell Proliferation - drug effects; Cellular biology; Chemokines - biosynthesis; Cytokines; Down-Regulation - drug effects; Humans; Interferon-beta - genetics; Interferon-beta - metabolism; Life Sciences; Lipopolysaccharides - pharmacology; Medical Biochemistry; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Myeloid Differentiation Factor 88 - metabolism; NF-kappa B - metabolism; Oncology; Osteogenesis - drug effects; Peptidoglycan - pharmacology; Proteins; Receptors, Cytokine - genetics; Receptors, Cytokine - metabolism; RNA, Small Interfering - metabolism; Stem cells; Toll-Like Receptors - agonists
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-008-9842-1

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-κB 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 IFNβ 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.