The roles of interleukin-10 (IL-10) have been emphasized in several models of glomerulonephritis (GN). Three biallelic polymorphisms within the IL-10 promoter region, at positions -1,082, -819, and -592 from the transcription initiation site, were shown to affect the level of IL-10 production. To investigate the effect of IL-10 promoter polymorphisms on the predisposition to development of GN in Korea, IL-10 promoter polymorphisms were assayed by polymerase chain reaction followed by restriction fragment length polymorphism in 108 patients with IgA nephropathy (IgAN), 49 focal segmental glomerulosclerosis (FSGS), and 100 healthy controls. In comparison with the control, the frequency of -1,082*G alleles were lower in IgAN and the frequencies of -592*C and -819*C were lower in FSGS, respectively. As for the haplotype, GCC haplotype was less frequent among IgAN than the control and ATA haplotype was more frequent among FSGS than the control (p<0.05). The frequency of intermediate producer genotypes (GCC/ACC and GCC/ATA) were lower among IgAN or FSGS than the control. Our findings suggested that IL-10 promoter polymorphism predisposed to the development of IgAN and FSGS in Korean patients.
Alleles ; Base Sequence ; Case-Control Studies ; DNA/genetics ; Gene Frequency ; Glomerulonephritis, IGA/*genetics/*immunology ; Glomerulosclerosis, Focal/*genetics/*immunology ; Haplotypes ; Humans ; Interleukin-10/*genetics ; Korea ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; *Promoter Regions (Genetics) ; Research Support, Non-U.S. Gov't

OBJECTIVETo study the expression of neonatal Fc receptor in podocytes in human nephritis and immune-induced rat nephritis models: anti-Thy1.1 nephritis and Heymann nephritis.

METHODSThirty-nine cases of renal biopsies were enrolled from September 2009 to February 2010, including 8 cases of minimal change disease, 4 cases of focal segmental glomerulosclerosis, 9 cases of membranous nephropathy, 12 cases of IgA nephropathy and 6 cases of lupus nephritis. Five normal kidney tissue samples adjacent to renal clear-cell carcinoma were served as normal controls. Laser capture microdissection and real-time RT-PCR were used to assess the expression level of FcRn mRNA in glomeruli of various glomerulonephritides, and immunohistochemistry (IHC) of FcRn by SuperVision method was performed. In addition, rat models of mesangial proliferative nephritis (anti-Thy1.1 nephritis) and passive membranous nephropathy (Heymann nephritis) were established and FcRn was examined in renal tissues by IHC.

RESULTSThe FcRn mRNA level in lupus nephritis was statistically higher than that of normal controls (P < 0.05). FcRn protein expression by IHC was seen in lupus nephritis (6/6), membranous nephropathy (6/9) and IgA nephropathy (7/12), significantly higher than that of normal controls (0/5), P < 0.05. Minimal change disease and focal segmental glomerular sclerosis showed minimal or none expression of FcRn (1/8, 0/4 respectively) and not statistically difference from that of normal controls. Furthermore, FcRn expression in podocytes was detected in rat anti-Thy1.1 (3/5) and Heymann nephritis models (2/7) but was not detected in normal controls.

CONCLUSIONSExpression of FcRn in podocytes was up-regulated in immune-induced human nephritis and rat nephritis models of anti-Thy1.1 nephritis and Heymann nephritis. FcRn may play a role in the development of immune-induced glomerulonephritis.

Animals ; Glomerulonephritis, IGA ; metabolism ; pathology ; Glomerulonephritis, Membranous ; metabolism ; pathology ; Glomerulosclerosis, Focal Segmental ; metabolism ; pathology ; Histocompatibility Antigens Class I ; genetics ; metabolism ; Humans ; Laser Capture Microdissection ; Lupus Nephritis ; metabolism ; pathology ; Male ; Nephritis ; genetics ; immunology ; metabolism ; pathology ; Nephrosis, Lipoid ; metabolism ; pathology ; Podocytes ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Receptors, Fc ; genetics ; metabolism ; Thy-1 Antigens ; immunology ; metabolism ; Up-Regulation