Local overexpression of interleukin-1 family, member 6 relates to the development of tubulointerstitial lesions

Abstract

Identification of factors that exacerbate a disease is important for the development of biomarkers. In this study, we discovered ectopic overexpression of interleukin-1 family, member-6 (IL-1F6) in several murine renal diseases. IL-1F6 participates in cytokine/chemokine production in the epithelium. In PCR array analysis for inflammatory mediators, Il1f6 showed the highest expression in the kidney of the B6.MRLc1 glomerulonephritis model. IL-1F6 was localized in the epithelium from the DCTs to CCDs, which showed tubular dilations or epithelial deciduations. Ultrastructual examination of the epithelial cells revealed that IL-1F6 was localized on the cytoplasmic ribosome, vesicles, and nucleus. In and around these tubules, we found infiltrations of CD3-positive T-cells and nestin-or a-smooth-muscle actin-positive mesenchymal cells. Expression of the IL-1F6 protein and Il1f6 mRNA in the kidney was increased by the development of TILs in the B6.MRLc1 model and in lupus (BXSB, NZB/WF1, and MRL/lpr), nephrotic syndrome (ICGN), and streptozotocin-induced diabetic models. IL-1F6 was also detected in the epithelia having squamous or deciduous contours in other organs such as the skin, esophagus, thymus, or uterus. In vitro analysis using M-1 cells from the murine collecting duct revealed that Il1f6 mRNA induction was related to the upregulation of IL-6, TGF-b receptor-1, and mesenchymal markers and to the downregulation of epithelial markers and changes in the squamous cells of the epithelium. Interestingly, urine Il1f6 mRNA expression was detected earlier than renal dysfunctions in these mouse models. Ectopic overexpression of IL-1F6 in kidneys is associated with TILs and especially with cell infiltrations and changes in epithelial morphology. We propose that local overexpression of IL-1F6 is related to the development of TILs.

Differential Gene Expression Profiling of Mouse Uterine Luminal Epithelium During Periimplantation

“…74 Gene Ontology annotation groups 5 genes into ''immune response'' subcategory, F3, Il1f6 (Interleukin 1 family, member 6), Kng1 (Kininogen 1), Mif (macrophage migration inhibitory factor), and Pla2g7 (phospholipase A2, group VII), which are all significantly upregulated in the D4.5 LE ( Figure 3E and F and Supplemental Table 2). Besides the role of F3 in coagulation and proinflammation, 45 IL1F6 participates in cytokine/ chemokine production 75 ; KNG1 is also involved in coagulation and proinflammation 76 ; MIF is a cytokine with chemokine-like functions mediating host immune and inflammatory response 77 ; and PLA2G7 metabolizes platelet-activating factor and its roles in immune responses seem to depend on the specific biological settings. 78 The upregulation of these ''immune response'' genes indicates increased inflammatory responses in the LE during the early stages of embryo implantation.…”

IL-36R ligands are potent regulators of dendritic and T cells

“…6 Elevated IL-36␣ mRNA and protein expression was reported also in chronic kidney disease. 16 Finally, in previous studies, we have shown that IL-36␤ mRNA is expressed in human rheumatoid synovial tissues and that synovial fibroblasts express IL-36R. 17 The in vivo effects of IL-36R ligands remain also poorly characterized.…”

Close Relations between Podocyte Injuries and Membranous Proliferative Glomerulonephritis in Autoimmune Murine Models

“…This congenic region contains the Fas ligand, interferon-activated gene 200 family, and the Fc gamma receptor family, which were strongly associated with the developments of autoimmunity and MPGN [18]. With age, female B6.MRL spontaneously develop MPGN similar to human CKD [18,19,20]. Therefore, we considered that BXSB- Yaa and B6.MRL as appropriate models for the investigation of podocyte injury in MPGN.…”