RESUMO
Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by CD1d. Invariant NKT cells (iNKT) correspond to >90% of the total population of NKTs and reacts to α-galactosylceramide (αGalCer). αGalCer promotes a complex mixture of Th1 and Th2 cytokines, as interferon (IFN)-γ and interleukin (IL)-4. NKT cells and IFN-γ are known to participate in some models of renal diseases, but further studies are still necessary to elucidate their mechanisms. The aim of our study was to analyze the participation of iNKT cells in an experimental model of tubule-interstitial nephritis. We used 8-wk-old C57BL/6j, Jα18KO and IFN-γKO mice. They were fed a 0.25% adenine diet for 10 d. Both adenine-fed wild-type (WT) and Jα18KO mice exhibited renal dysfunction, but adenine-fed Jα18KO mice presented higher expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF)-α and type I collagen. To analyze the role of activated iNKT cells in our model, we administered αGalCer in WT mice during adenine ingestion. After αGalCer injection, we observed a significant reduction in serum creatinine, proinflammatory cytokines and renal fibrosis. However, this improvement in renal function was not observed in IFN-γKO mice after αGalCer treatment and adenine feeding, illustrating that this cytokine plays a role in our model. Our findings may suggest that IFN-γ production is one of the factors contributing to improved renal function after αGalCer administration.
Assuntos
Galactosilceramidas/administração & dosagem , Interferon gama/genética , Nefrite/tratamento farmacológico , Insuficiência Renal/tratamento farmacológico , Adenina/toxicidade , Animais , Antígenos CD1d/biossíntese , Antígenos CD1d/genética , Colágeno Tipo I/biossíntese , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Interleucina-4/biossíntese , Interleucina-4/genética , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Células T Matadoras Naturais/efeitos dos fármacos , Células T Matadoras Naturais/imunologia , Nefrite/induzido quimicamente , Nefrite/genética , Nefrite/patologia , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/genética , Insuficiência Renal/patologia , Fator de Necrose Tumoral alfa/biossínteseRESUMO
B lymphocyte infiltration in renal acute allograft rejection has been associated with steroid resistance and poor outcomes. We aimed to measure CD20 mRNA in urine of renal transplant patients with graft dysfunction and correlate with the histological diagnosis and immunohistochemical (IH) staining for CD20. A total of 48 urine samples were analyzed (21 with acute rejection, 10 with chronic allograft nephropathy, 11 with unspecific tubular lesions, 3 with acute pyelonephritis and 3 with polyomavirus nephropathy). Higher urinary CD20 levels associated with a positive IH staining for CD20 (>50 positive cells/HPF) in renal tissue (p=0.04), with a sensitivity of 83.3% and a specificity of 51.6%. Within the acute rejection group, a positive staining for CD20 was not associated with graft loss, steroid resistance or lack of return to basal creatinine after treatment, but was associated with higher serum creatinine at 3 and 6 months, 1 and 2 years after the acute episode (p<0.05). In conclusion, we showed that urinary levels of CD20 detected by RT-PCR had a high sensitivity for CD20+ staining in the corresponding renal tissue, but with a low specificity. Patients with clusters of CD20+ cells >50/HPF had higher serum creatinine after 2 years of follow up.
Assuntos
Antígenos CD20/biossíntese , Linfócitos B/imunologia , Rejeição de Enxerto/urina , Transplante de Rim/imunologia , RNA Mensageiro/urina , Doença Aguda , Adulto , Linfócitos B/metabolismo , Biomarcadores/urina , Doença Crônica , Creatinina/sangue , Creatinina/urina , Feminino , Rejeição de Enxerto/patologia , Humanos , Transplante de Rim/patologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Transplante Homólogo/imunologia , Transplante Homólogo/patologiaRESUMO
INTRODUCTION: Toll-like receptors (TLR) comprehend an emerging family of receptors that recognize pathogen-associated molecular patterns and promote the activation of leukocytes. Surgical trauma and ischemia-reperfusion injury are likely to provide exposure to endogenous ligands for TLR in virtually all kidney transplant recipients. METHODS: Macroarray (GEArray OHS-018.2 Series-Superarray) analyses of 128 genes involved in TLR signaling pathway were performed in nephrectomy samples of patients with chronic allograft nephropathy (CAN) and acute rejection (AR, vascular and non vascular). The analysis of each membrane was performed by GEArray Expression Analysis Suite 2.0. RESULTS: Macroarray profile identified a gene expression signature that could discriminate CAN and AR. Three genes were significantly expressed between CAN and vascular AR: Pellino 2; IL 8 and UBE2V1. In relation to vascular and non-vascular AR, there were only two genes with statistical significance: IL-6 and IRAK-3. CONCLUSION: Vascular and non-vascular AR and CAN showed different expression of a few genes in TLR pathway. The analysis of nephrectomy showed that activation of TLR pathway is present in AR and CAN.
