title: TREM-1 regulates macrophage polarization in ureteral obstruction.
abstract: Chronic kidney disease (CKD) is an emerging worldwide public health problem. Inflammatory cell infiltration and activation during the early stages in injured kidneys is a common pathologic feature of CKD. Here, we determined whether an important inflammatory regulator, triggering receptor expressed on myeloid cells (TREM)-1, is upregulated in renal tissues collected from mouse ureteral obstruction-induced nephritis. TREM-1 is crucial for modulating macrophage polarization, and has a pivotal role in mediating tubular injury and interstitial collagen deposition in obstructive nephritis. Lysates from nephritic kidneys triggered a TREM-1-dependent M1 polarization ex vivo, consistent with the observation that granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived M1 macrophages express higher levels of TREM-1 in comparison with M-CSF-derived cells. Moreover, agonistic TREM-1 cross-link significantly strengthens the inductions of iNOS and GM-CSF in M1 cells. These observations are validated by a strong clinical correlation between infiltrating TREM-1-expressing/iNOS-positive macrophages and renal injury in human obstructive nephropathy. Thus, TREM-1 may be a potential diagnostic and therapeutic target in human kidney disease.
authors.affiliation: Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan (ROC).
authors.forename: Tzu-Han
authors.initials: TH
authors.lastname: Lo
authors.affiliation: Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan (ROC).
authors.forename: Kai-Yu
authors.initials: KY
authors.lastname: Tseng
authors.affiliation: Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan (ROC).
authors.forename: Wen-Shan
authors.initials: WS
authors.lastname: Tsao
authors.affiliation: 1] Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan (ROC) [2] Genomic Research Center, Academia Sinica, Taipei, Taiwan (ROC).
authors.forename: Chih-Ya
authors.initials: CY
authors.lastname: Yang
authors.affiliation: 1] Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan (ROC) [2] Genomic Research Center, Academia Sinica, Taipei, Taiwan (ROC) [3] Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (ROC) [4] Inflammation and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan (ROC) [5] Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan (ROC) [6] Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shie-Liang
authors.initials: SL
authors.lastname: Hsieh
authors.affiliation: Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan (ROC).
authors.forename: Allen Wen-Hsiang
authors.initials: AW
authors.lastname: Chiu
authors.affiliation: Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.affiliation: 1] Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan (ROC) [2] Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (ROC) [3] Inflammation and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan (ROC) [4] Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan (ROC) [5] Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (ROC).
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Tarng
authors.affiliation: 1] Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan (ROC) [2] Inflammation and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan (ROC).
authors.forename: Nien-Jung
authors.initials: NJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation; D016764:Cell Polarity; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009393:Nephritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D015854:Up-Regulation; D014517:Ureteral Obstruction / Q000150:complications / Q000378:metabolism* / Q000473:pathology
chemical_list: D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D052247:Nitric Oxide Synthase Type II