title: Role of IRAK1 on TNF-induced proliferation and NF-ĸB activation in human bone marrow mesenchymal stem cells.
abstract: In this study, we determined the effect of TNF-α on hBMSCs proliferation as well as the role of IL-1 receptor-associated kinase 1 (IRAK1) on TNF-α signaling. Western blot analysis revealed that TNF-α treatment increased the phosphorylation of IRAK1 in hBMSCs. The downregulation of IRAK1 inhibited TNF-α-induced NF-ĸB activation and COX-2 expression. TNF-α treatment increased hBMSCs proliferation in a dose-dependent manner and increased ERK, JNK, and NF-ĸB activity. U0126, an ERK inhibitor, decreased hBMSCs proliferation and significantly blocked TNF-α -induced hBMSCs proliferation. In cells with IRAK1 or TRADD downregulation, the U0126 treatment inhibited hBMSCs proliferation and significantly suppressed TNF-α-induced hBMSCs proliferation. The downregulation of IRAK1 or TRADD inhibited TNF-α-induced ERK and JNK activation, and hBMSCs proliferation. Inhibition of NF-ĸB by decoy oligonucleotides reduced the TNF-α-induced hBMSCs proliferation. Immunoprecipitation analysis showed that IRAK1 does not physically interact with TNF receptor 1 (TNFR1) even in the presence of TNF-α. Suppression of IRAK1 binding protein (IRAK1BP1) inhibited TNF-α-induced increase of the proliferation and ERK1 phosphorylation of hBMSCs in the presence of TNF-α. Our data indicate that TNF-α modulates hBMSCs proliferation through ERK signaling pathways, and that IRAK1 plays an important role in TNF-α-induced NF-ĸB activation in hBMSCs.
authors: Department of Physiology, School of Medicine, Pusan National University, Yangsan, Korea.
authors: Jong Myung
authors: JM
authors: Kim
authors: Hyun Hwa
authors: HH
authors: Cho
authors: Sun Young
authors: SY
authors: Lee
authors: Chang Pyo
authors: CP
authors: Hong
authors: Ji won
authors: Jw
authors: Yang
authors: You Sun
authors: YS
authors: Kim
authors: Kuen Tak
authors: KT
authors: Suh
authors: Jin Sup
authors: JS
authors: Jung
mesh_terms: D001854:Bone Marrow Cells / Q000378:metabolism* / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D053199:TNF Receptor-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D047428:Protein Kinase Inhibitors; D047888:Receptors, Tumor Necrosis Factor, Type I; D053199:TNF Receptor-Associated Death Domain Protein; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; D020928:Mitogen-Activated Protein Kinases