Browse > Article
http://dx.doi.org/10.3339/jkspn.2018.22.1.22

Interleukin-13 Increases Podocyte Apoptosis in Cultured Human Podocytes  

Lee, Keum Hwa (Department of Pediatrics, Yonsei University College of Medicine)
Oh, Ji Young (Department of Pediatrics, Yonsei University College of Medicine)
Seong, Su-Bin (Department of Pediatrics, Chungbuk National University College of Medicine)
Ha, Tae-Sun (Department of Pediatrics, Chungbuk National University College of Medicine)
Shin, Jae Il (Department of Pediatrics, Yonsei University College of Medicine)
Publication Information
Childhood Kidney Diseases / v.22, no.1, 2018 , pp. 22-27 More about this Journal
Abstract
Purpose: Podocytes are important architectures that maintain the crucial roles of glomerular filtration barrier functions. Despite this structural importance, however, the mechanisms of the changes in podocytes that can be an important pathogenesis of minimal change nephrotic syndrome (MCNS) are not clear yet. The aim of this study was to investigate whether apoptosis is induced by interleukin (IL)-13 in cultured human podocytes. Methods: Human podocytes were treated with different IL-13 doses and apoptotic cells were analyzed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay) and fluorescence-activated cell sorting (FACS). Results: The IL-13 increased the number of TUNEL-positive cells in a dose-dependent manner at 6 and 18 hours (P<0.05 and P<0.05, respectively). The apoptosis rate was appeared to be increased slightly in the IL-13-stimulated podocytes (8.63%, 13.02%, and 14.46%; 3, 10 and 30 ng/mL, respectively) than in the control cells (7.66%) at 12 hours by FACS assay. Conclusion: Our study revealed that IL-13 expression may increase podocyte apoptosis. Blocking the IL-13 signal pathway can potentially play an important role in regulating the apoptosis of podocytes.
Keywords
Interleukin (IL)-13; Podocytes; Apoptosis; Minimal change nephrotic syndrome (MCNS);
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Churg J, Habib R, White RH. Pathology of the nephrotic syndrome in children: a report for the International Study of Kidney Disease in Children. Lancet 1970;760:1299-30.
2 Haas M, Meehan SM, Karrison TG, Spargo BH. Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis 1997;30:621.   DOI
3 Friedrich K, Brandlein S, Ehrhardt I, Krause S, Luttmann W. Interleukin- 4 and Interleukin-13 receptors trigger distinct JAK/STAT activation patterns in mouse lymphocytes. Signal Transduction 2003;3:26-32.   DOI
4 Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr. Prognostic significance of the early course of minimal change nephrotic syndrome: Report of the International Study of Kidney Disease in Children. J Am Soc Nephrol 1997;8:769-76.
5 Trompeter RS, Lloyd BW, Hicks J, White RH, Cameron JS. Longterm outcome for children with minimal-change nephrotic syndrome. Lancet 1985;1:368-70.
6 A report of the International Study of Kidney Disease in Children. The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr 1981;98:561-4.   DOI
7 Teeninga N, Kist-van Holthe JE, van Rijswijk N, de Mos NI, Hop WC, Wetzels JF, et al. Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome. J Am Soc Nephrol 2013; 24:149-59.   DOI
8 Gipson DS, Chin H, Presler TP, Jennette C, Ferris ME, Massengill S, et al. Differential risk of remission and ESRD in childhood FSGS. Pediatr Nephrol 2006;21:344-9.   DOI
9 D'Agati VD. Pathologic classification of focal segmental glomerulosclerosis. Semin Nephrol 2003;23:117-34.   DOI
10 Schnaper HW. Idiopathic focal segmental glomerulosclerosis. Semin Nephrol 2003;23:183-93.   DOI
11 Pavenstadt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev 2002;83:253-307.
12 Asanuma K, Mundel P. The role of podocytes in glomerular pathobiology. Clin Exp Nephrol 2003;7:255-9.   DOI
13 McKenzie AN, Culpepper JA, de Waal Malefyt R, Briere F, Punnonen J, Aversa G, et al. Interleukin 13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. Proc Natl Acad Sci USA 1993; 90:3735-40.   DOI
14 Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of pro-grammed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 1992;119:493-501.   DOI
15 Cheung W, Wei CL, Seah CC, Jordan SC, Yap HK. Atopy, serum IgE, and interleukin-13 in steroid-responsive nephrotic syndrome. Pediatr Nephrol 2004;19:627-32.   DOI
16 Park SJ, Saleem MA, Nam JA, Ha TS, Shin JI. Effects of interleukin-13 and montelukast on the expression of zonula occludens-1 in human podocytes. Yonsei Med J 2015;56:426-32.   DOI
17 Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 1995;146:3-15.
18 Lai KW, Wei CL, Tan LK, Tan PH, Chiang GS, Lee CG, et al. Overexpression of interleukin-13 induces minimal-change-like nephropathy in rats. J Am Soc Nephrol 2007;18:1476-85.   DOI
19 Ha TS, Nam JA, Seong SB, Saleem MA, Park SJ, Shin JI. Montelukast improves the changes of cytoskeletal and adaptor proteins of human podocytes by interleukin-13. Inflamm Res 2017;66:793-802.   DOI
20 Yap HK, Cheung W, Murugasu B, Sim SK, Seah CC, Jordan SC. Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: evidence for increased IL-13 mRNA expression in relapse. J Am Soc Nephrol 1999;10:529-37.
21 Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev 2007;87:99-163.   DOI
22 Ryu M, Mulay SR, Miosge N, Gross O, Anders HJ. Tumour necrosis factor-alpha drives Alport glomerulosclerosis in mice by promoting podocyte apoptosis. J Pathol 2011;226:120-31.
23 Zou H, Henzel WJ, Liu X, Lutschg A, Wang X. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 1997;90:405-13.   DOI
24 Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, et al. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ 2012;19:107-20.   DOI
25 Faleiro L, Kobayashi R, Fearnhead H, Lazebnik Y. Multiple species of CPP32 and Mch2 are the major active caspases present inapoptotic cells. EMBO J 1997;16:2271-81.   DOI
26 Polverino AJ and Patterson SD. Selective activation of caspases during apoptotic induction in HL-60 cells. J Biol Chem 1997;272: 7013-21.   DOI
27 Manna SK, Aggarwal BB. IL-13 suppresses TNF-induced activation of nuclear factor-kappa B, activation protein-1, and apoptosis. J Immunol 1998;161:2863-72.
28 Kawakami M, Kawakami K, Puri RK. Apoptotic pathways of cell death induced by an interleukin-13 receptor-targeted recombinant cytotoxin in head and neck cancer cells. Cancer Immunol Immunother 2002;50:691-700.   DOI
29 Kawakami M, Kawakami K, Puri RK. Tumor regression mechanisms by IL-13 receptor-targeted cancer therapy involve apoptotic pathways. Int J Cancer 2003;103:45-52.   DOI
30 Borowski A, Kuepper M, Horn U, Knupfer U, Zissel G, Hohne K, et al. Interleukin-13 acts as an apoptotic effector on lung epithelial cells and induces pro-fibrotic gene expression in lung fibroblasts. Clin Exp Allergy 2008;38:619-28.   DOI
31 Heller F, Fromm A, Gitter AH, Mankertz J, Schulzke JD. Epithelial apoptosis is a prominent feature of the epithelial barrier disturbance in intestinal inflammation: effect of pro-inflammatory interleukin-13 on epithelial cell function. Mucosal Immunol 2008;1 Suppl 1:S58-61.