title: Oxalate upregulates expression of IL-2Rβ and activates IL-2R signaling in HK-2 cells, a line of human renal epithelial cells.
abstract: The role of inflammation in oxalate-induced nephrolithiasis is debated. Our gene expression study indicated an increase in interleukin-2 receptor β (IL-2Rβ) mRNA in response to oxalate (Koul S, Khandrika L, Meacham RB, Koul HK. PLoS ONE 7: e43886, 2012). Herein, we evaluated IL-2Rβ expression and its downstream signaling pathway in HK-2 cells in an effort to understand the mechanisms of oxalate nephrotoxicity. HK-2 cells were exposed to oxalate for various time points in the presence or absence of SB203580, a specific p38 MAPK inhibitor. Gene expression data were analyzed by Ingenuity Pathway Analysis software. mRNA expression was quantitated via real-time PCR, and changes in protein expression/kinase activation were analyzed by Western blotting. Exposure of HK-2 cells to oxalate resulted in increased transcription of IL-2Rβ mRNA and increased protein levels. Oxalate treatment also activated the IL-2Rβ signaling pathway (JAK1/STAT5 phosphorylation). Moreover, the increase in IL-2Rβ protein was dependent upon p38 MAPK activity. These results suggest that oxalate-induced activation of the IL-2Rβ pathway may lead to a plethora of cellular changes, the most common of which is the induction of inflammation. These results suggest a central role for the p38 MAPK pathway in mediating the effects of oxalate in renal cells, and additional studies may provide the key to unlocking novel biochemical targets in stone disease.
authors: Dept. of Biochemistry and Molecular Biology, LSU Health Sciences Center, 1501 Kings Highway, PO Box 33932, Shreveport, LA 71130-3932. hkoul@lsuhsc.edu.
authors: Sweaty
authors: S
authors: Koul
authors: Lakshmipathi
authors: L
authors: Khandrika
authors: Thomas J
authors: TJ
authors: Pshak
authors: Naoko
authors: N
authors: Iguchi
authors: Mintu
authors: M
authors: Pal
authors: Joshua J
authors: JJ
authors: Steffan
authors: Hari K
authors: HK
authors: Koul
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053646:Interleukin-2 Receptor beta Subunit / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D053613:Janus Kinase 1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009393:Nephritis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D019815:Oxalic Acid / Q000633:toxicity*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C508020:IL2RB protein, human; D018836:Inflammation Mediators; D053646:Interleukin-2 Receptor beta Subunit; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D019815:Oxalic Acid; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases
keywords: IL-2R; inflammation; kidney stones; oxalate, p38 MAPK