title: Regulation of TLR2 and NLRP3 in primary murine renal tubular epithelial cells.
abstract: Pattern recognition receptors (PRRs) are now recognized to be key triggers of injury in a variety of renal diseases. Several families of these receptors are present in the kidney, and recent data suggest that they are differentially expressed and regulated in the kidney. This study evaluated the interaction between two distinct PRRs that are expressed in the kidney, i.e. TLR2 (Toll-like receptor 2) and the NLRP3 inflammasome. The regulation and activation of these receptors in primary renal tubular epithelial (RTE) cells from murine kidneys were evaluated. RTE cells were extracted from WT and NLRP3-mutant mice and treated ex vivo with ligands specific for TLR2 or NLRP3. We found that TLR2 upregulated NLRP3 as well as its substrate IL-1β, and that signaling through the NLRP3 inflammasome induced RTE cell necrosis. The results of this study suggest a previously unknown interaction between TLR2 and NLRP3 in primary RTE cells and highlight the importance of the cross talk that occurs in kidney-related PRRs. Understanding how PRRs are regulated is important for the design of rationale therapeutic strategies to modulate these receptors in renal disease.
authors.affiliation: Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, Calif., USA.
authors.forename: Sashi G
authors.initials: SG
authors.lastname: Kasimsetty
authors.forename: Sean E
authors.initials: SE
authors.lastname: DeWolf
authors.forename: Alana A
authors.initials: AA
authors.lastname: Shigeoka
authors.forename: Dianne B
authors.initials: DB
authors.lastname: McKay
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D058847:Inflammasomes / Q000502:physiology*; D053583:Interleukin-1beta / Q000502:physiology; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D008024:Ligands; D008074:Lipoproteins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009336:Necrosis; D009550:Nigericin / Q000494:pharmacology; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D008024:Ligands; D008074:Lipoproteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine; D000255:Adenosine Triphosphate; D009550:Nigericin