| First Author | Ichii O | Year | 2017 |
| Journal | Front Immunol | Volume | 8 |
| Pages | 1346 | PubMed ID | 29109726 |
| Mgi Jnum | J:268849 | Mgi Id | MGI:6272457 |
| Doi | 10.3389/fimmu.2017.01346 | Citation | Ichii O, et al. (2017) IL-36alpha Regulates Tubulointerstitial Inflammation in the Mouse Kidney. Front Immunol 8:1346 |
| abstractText | IL-36alpha, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36alpha was overexpressed in injured distal tubules (DTs); however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO) or folic acid (FA) injection was performed in mouse kidneys to assess the role of IL-36alpha in kidney injury. IL-36alpha mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36alpha localized to dilated DTs. IL-36alpha expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice. At 24 h after UUO, IL-36alpha(+) DT epithelial cells showed loose intercellular digitations. IL-1RL2, an IL-36alpha receptor protein, localized to podocytes, proximal tubules, and DTs in the healthy kidney. IL-1RL2 was expressed in interstitial cells and platelets or extended primary cilia of DT epithelial cells in UUO kidneys. IL-36alpha stimulation promoted the production of IL-6 and Prss35, an inflammatory cytokine and collagen remodeling-associated enzyme, respectively, in cultured NIH3T3 fibroblasts. UUO-treated IL-36alpha-knockout (KO) mice showed milder kidney injury features than wild-type (WT) mice did. In UUO kidneys from IL-36alpha-KO mice, the expression of genes associated with inflammatory response and sensory perception was significantly different from that in WT mice. Altogether, our data indicate an association between intrarenal IL-36alpha overexpression and the progression of tubulointerstitial inflammations and morpho-functional alterations of DT epithelial cells. IL-36alpha may be a novel kidney injury marker useful for evaluating DT damages. |
