Expression of TLR2, NOD1, and NOD2 and the NLRP3 Inflammasome in Renal Tubular Epithelial Cells of Male versus Female Mice.

Background: Gender-biased outcomes are associated with acute kidney injury (AKI) and human and animal studies have shown that females are preferentially protected from renal ischemia. However, the reason for this is not known. One clue might lie with pattern recognition receptors (PRRs), which are triggers of ischemic injury when ligated by molecules in the ischemic milieu. Several PRR families are expressed by renal tubular epithelial cells (RTEs) and incite cell death signaling and production of pro-inflammatory molecules. Blockade of specific PRRs (e.g., TLR2, NOD1, NOD2, and NLRP3) provides highly significant protection from ischemic RTE injury. As a first step to understand gender-biased outcomes of AKI, we tested whether constitutive gender-based differences exist in expression of these PRRS in RTEs.

Methods: To determine whether PRR expression differences exist, primary RTEs isolated from male and female WT kidneys were examined by FACS, qPCR, and Western Blot for expression of TLR2, NOD1, NOD2, and NLRP3 inflammasome components.

Results: No RTE gender-based differences in TLR2, NOD1, NOD2, NLRP3, or ASC were found. RTEs from female kidneys had approximately half the mRNA, but the same protein concentration of pro-caspase-1 compared to RTEs isolated from male kidneys.

Conclusions: Our findings indicate that intrinsic gender differences in RTE expression of TLR2, NOD1, NOD2, NLRP3, and ASC are not responsible for the gender-biased outcomes observed in ischemia/reperfusion injury. The lower caspase-1 mRNA expression in RTEs from females warrants further exploration of additional upstream signals that might differentially regulate caspase-1 in male vs. female RTEs.