interleukin-8 and Kidney-Calculi

Urolithiasis is one of the most common urological diseases worldwide with an unclear aetiology. However, a growing body of evidence suggests the potential role of molecular disturbances of the inflammation as well as oxidative and nitrative stresses, in the pathogenesis of urolithiasis. Therefore, we aimed to detect the potential association between six selected single-nucleotide polymorphisms (SNPs) and the development of nephrolithiasis. Moreover, we verified the association of urolithiasis development and mRNA expression of IL-6, IL-8, SOD2, and NOS2 in peripheral blood mononuclear cells (PBMCs). Total genomic DNA and mRNA were isolated from the peripheral blood of 112 patients with urolithiasis and 114 healthy subjects. Using Taq-Man® probes, we genotyped the following SNPs: rs1800797 and rs2069845 in IL-6, rs2227307 in IL-8, rs4880 in SOD2, rs2297518 and rs2779249 in NOS2. In turn, the evaluation of mRNA expression was performed using real-time PCR and 2-ΔCt methods. We found that the C/T genotype of the c.47 T>C-SOD2 SNP increased the frequency of urolithiasis occurrence whereas the T/T homozygote of the same polymorphism decreased the risk of urolithiasis development in the Polish population. Moreover, our study confirmed that patients with urolithiasis were characterised by decreased IL-6, IL-8, and SOD2 mRNA expression levels compared to the controls. In conclusion, our results suggest that polymorphic variants and changes in mRNA expression of IL-6, IL8, SOD2, and NOS2 may be involved in the pathophysiology of urolithiasis.

Topics: Case-Control Studies; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-6; Interleukin-8; Kidney Calculi; Leukocytes, Mononuclear; Oxidative Stress; Polymorphism, Single Nucleotide; RNA, Messenger; Urolithiasis

Deposition of calcium oxalate (CaOx) crystals in renal interstitium is one of the key factors that cause progressive inflammation in kidney stone disease. Macrophages are responsible for elimination of these crystals but their roles to worsen inflammatory process remain under-investigated. This study thus aimed to define roles of exosomes released from macrophages exposed to CaOx crystals in mediating subsequent inflammatory cascades. Macrophages were incubated with or without CaOx monohydrate (COM) crystals for 16 h and their exosomes were isolated. Quantitative proteomics using nanoLC-ESI-Qq-TOF MS/MS revealed 26 proteins with significantly altered levels in exosomes derived from COM-treated macrophages (COM-treated exosomes) comparing to those derived from the controlled macrophages (controlled exosomes). Protein network analysis showed that these altered proteins were involved in cytoskeleton and actin binding, calcium binding, stress response, transcription regulation, immune response and extracellular matrix disassembly. Functional investigations revealed that COM-treated exosomes enhanced IL-8 production from renal tubular cells, activated neutrophil migration, had increased (exosomal) membrane fragility, had greater binding capacity to COM crystals, and subsequently enhanced crystal invasion through extracellular matrix migration chamber. These data indicate that macrophage exosomes play important roles in inflammatory response to COM crystals and may be involved in crystal invasion in the renal interstitium.

Topics: Animals; Calcium Oxalate; Cell Movement; Dogs; Exosomes; Extracellular Matrix; Humans; Interleukin-8; Kidney; Kidney Calculi; Kidney Tubules; Macrophages; Madin Darby Canine Kidney Cells; Neutrophils; Proteome; U937 Cells

Topics: Animals; Case-Control Studies; Chemokine CCL2; Child; Child, Preschool; China; Female; Food Contamination; Hong Kong; Humans; Interleukin-8; Kidney; Kidney Calculi; Male; Milk; Triazines; Ultrasonography