interleukin-8 and Glomerulonephritis--Membranous

Low-density lipoprotein apheresis (LDL-A) treatment combined with steroids demonstrated significant improvement of nephrotic proteinuria in steroid- or immunosuppressive-resistant patients from focal and segmental glomerulosclerosis (FGS). The mechanisms of the effect of LDL-A in nephrotic syndrome (NS) are unknown, but a reduction in inflammatory cytokines and chemokines secreted from macrophages has been supposed.. Serum levels of interleukin (IL)-8, tumor necrosis factor-alpha (TNF-alpha), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay in 27 patients with NS [13 with FGS and 14 with minimal change nephrotic syndrome (MCNS)] before and after LDL-A and in 13 age-matched, healthy controls. We also selected three FGS patients who were resistant to steroid therapy for at least one month and who had undergone six LDL-A procedures. The effects of steroids and LDL-A on the production of IL-8, TNF-alpha, and MCP-1 by peripheral blood mononuclear cells (PBMCs) were also determined in some patients.. In NS, the serum levels of IL-8 and TNF-alpha, but not MCP-1, were significantly higher than in healthy controls. After LDL-A, IL-8 and TNF-alpha tended to decrease. IL-8 production by lipopolysaccharide (LPS)-stimulated PBMC, mainly adherent cells, was significantly reduced in both the steroid-resistant FGS group and nontreated NS group compared with controls, but TNF-alpha production was reduced in the only FGS group. After LDL-A, only IL-8 production recovered to the control group level.. Significant amelioration of IL-8 production independent of any effect of steroids on LPS-stimulated PBMCs may reflect a beneficial effect of LDL-A in normalizing the function of circulating monocytes in steroid-resistant FGS.

Topics: Blood Component Removal; Chemokine CCL2; Drug Resistance; Female; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Interleukin-8; Leukocytes, Mononuclear; Lipoproteins, LDL; Male; Nephrotic Syndrome; Steroids; Tumor Necrosis Factor-alpha

Biomarkers required to assess accurately the prognosis of idiopathic membranous nephropathy (IMN) are still unavailable. A retrospective study on 156 IMN patients showed only urinary IL-8 was associated with the achievement of initial complete remission (CR) in IMN patients. A urinary IL-8 level of less than 61.25 pg/mL was more sensitive for prediction of CR in IMN patients. Therefore, urinary IL-8 may be a potential biomarker for evaluating short-term prognosis of IMN patients.

Topics: Adult; Biomarkers; Cohort Studies; Female; Glomerulonephritis, Membranous; Humans; Interleukin-8; Male; Middle Aged; Prognosis; Retrospective Studies; Young Adult

Interleukin-8 (IL-8) is considered a deleterious chemokine involved in renal injury in glomerulonephritis (GN). IL-8 may be released as a 77-amino acid (AA) peptide or 72-AA protein.. We evaluated gene and protein expression of IL-8 in 53 renal biopsy specimens from patients with GN and 9 control kidneys. Nonradioactive in situ hybridization and reverse-transcriptase polymerase chain reaction (RT-PCR) were applied to detect IL-8 messenger RNA (mRNA). In immunohistochemistry, a double-staining technique with the use of antibodies against the 77-AA and 72-AA forms of IL-8, as well as glomerular cell antigens, was used.. By in situ hybridization, IL-8 mRNA was detected in normal glomerular, tubular, and some interstitial cells. The RT-PCR study showed that IL-8 mRNA expression in control kidneys significantly exceeds that in specimens with GN (0.89 +/- 0.82 versus 0.21 +/- 0.20; P < 0.003). In control kidneys, major sources of 77-AA IL-8 were podocytes and endothelial cells of interstitial vessels, whereas tubular epithelial cells expressed minute amounts of 72-AA IL-8. In GN specimens, podocyte expression of 72-AA IL-8 varied notably, with the greatest level found in minimal change disease and the lowest level found in acute endocapillary GN. Conversely, increased glomerular expression of the 72-AA form of IL-8 was a general feature of GN, with its level significantly exceeding that of the 77-AA form in acute endocapillary GN (P < 0.01).. Our results suggest that intrinsic glomerular cell production of IL-8, in particular the 77-AA form, may be relevant for preservation of the glomerular architecture.

Topics: Anti-Glomerular Basement Membrane Disease; Biopsy; Gene Expression Regulation; Glomerulonephritis; Glomerulonephritis, IGA; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Immunohistochemistry; In Situ Hybridization; Interleukin-8; Kidney Glomerulus; Lupus Nephritis; RNA, Messenger

Chemokines and their receptors play an important role in the pathogenesis of acute and chronic glomerular inflammation. However, their expression pattern and function in glomerular podocytes, the primary target cells in a variety of glomerulopathies, have not been investigated as of yet. Using RT-PCR, we now demonstrate the expression of CCR4, CCR8, CCR9, CCR10, CXCR1, CXCR3, CXCR4, and CXCR5 in cultured human podocytes. Stimulation of these receptors induced a concentration-dependent biphasic increase of the free cytosolic calcium concentration in podocytes in culture. In addition, we demonstrate that podocytes release IL-8 in the presence of FCS and that IL-8 down-regulates cell surface CXCR1. Chemokine stimulation of the detected CCRs and CXCRs increased activity of NADPH-oxidase, the primary source of superoxide anions in podocytes. Immunohistochemistry studies revealed only diffuse and weak CXCR expression in healthy human glomerula. In contrast, in membranous nephropathy, a characteristic podocyte disorder, the expression of CXCR1, CXCR3, and CXCR5 is up-regulated in podocytes. In conclusion, podocytes in culture and podocytes in human kidney sections express a set of chemokine receptors. The release of oxygen radicals that accompanies the activation of CCRs and CXCRs may contribute to podocyte injury and the development of proteinuria during membranous nephropathy.

Topics: Calcium; Cations, Divalent; Cell Line, Transformed; Cells, Cultured; Cytosol; Fluorescent Antibody Technique; Glomerulonephritis, Membranous; Humans; Immunohistochemistry; Interleukin-8; Kidney Glomerulus; Ligands; Receptors, Chemokine; Receptors, CXCR3; Receptors, CXCR4; Receptors, CXCR5; Receptors, Cytokine; Receptors, Interleukin-8A; Receptors, Interleukin-8B; RNA, Messenger; Serum Albumin, Bovine; Superoxides