TREM-1 regulates macrophage polarization in ureteral obstruction

Tzu Han Lo, Kai Yu Tseng, Wen Shan Tsao, Chih Ya Yang, Shie Liang Hsieh, Allen Wen Hsiang Chiu, Toshiyuki Takai, Tak W. Mak*, Der Cherng Tarng, Nien Jung Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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.

Original languageEnglish
Pages (from-to)1174-1186
Number of pages13
JournalKidney International
Volume86
Issue number6
DOIs
StatePublished - 1 Jan 2014

Keywords

  • Chronic kidney disease
  • Fibrosis
  • Immunology and pathology
  • Macrophages
  • Obstructive nephropathy

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