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Immunomodulatory Molecule IRAK-M Balances Macrophage Polarization and Determines Macrophage Responses during Renal Fibrosis.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2017 Aug 15; Vol. 199 (4), pp. 1440-1452. Date of Electronic Publication: 2017 Jul 12. - Publication Year :
- 2017
-
Abstract
- Activation of various innate immune receptors results in IL-1 receptor-associated kinase (IRAK)-1/IRAK-4-mediated signaling and secretion of proinflammatory cytokines such as IL-12, IL-6, or TNF-α, all of which are implicated in tissue injury and elevated during tissue remodeling processes. IRAK-M, also known as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression in intrarenal macrophages. Innate immune activation contributes to both acute kidney injury and tissue remodeling that is associated with chronic kidney disease (CKD). Our study assessed the contribution of macrophages in CKD and the role of IRAK-M in modulating disease progression. To evaluate the effect of IRAK-M in chronic renal injury in vivo, a mouse model of unilateral ureteral obstruction (UUO) was employed. The expression of IRAK-M increased within 2 d after UUO in obstructed compared with unobstructed kidneys. Mice deficient in IRAK-M were protected from fibrosis and displayed a diminished number of alternatively activated macrophages. Compared to wild-type mice, IRAK-M-deficient mice showed reduced tubular injury, leukocyte infiltration, and inflammation following renal injury as determined by light microscopy, immunohistochemistry, and intrarenal mRNA expression of proinflammatory and profibrotic mediators. Taken together, these results strongly support a role for IRAK-M in renal injury and identify IRAK-M as a possible modulator in driving an alternatively activated profibrotic macrophage phenotype in UUO-induced CKD.<br /> (Copyright © 2017 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Cytokines immunology
Disease Models, Animal
Disease Progression
Fibrosis pathology
Humans
Immunomodulation
Inflammation pathology
Interleukin-1 Receptor-Associated Kinases deficiency
Interleukin-1 Receptor-Associated Kinases genetics
Kidney immunology
Mice
Mice, Inbred C57BL
Signal Transduction
Tumor Necrosis Factor-alpha immunology
Ureteral Obstruction pathology
Fibrosis immunology
Interleukin-1 Receptor-Associated Kinases immunology
Kidney pathology
Macrophage Activation
Macrophages cytology
Macrophages immunology
Renal Insufficiency, Chronic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 199
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 28701510
- Full Text :
- https://doi.org/10.4049/jimmunol.1601982