Human bone marrow derived mesenchymal stromal/stem cells attenuate tubular inflammation upon albumin challenge

Abstract

BACKGROUND: Emerging evidence indicates that bone marrow derived mesenchymal stem cells (BM-MSC) protect against many forms of chronic renal diseases (CKD). The mechanism underlying this effect is not completely understood. We have previously shown the tubular expression of proinflammatory mediators induced by proteinuria play a vital role in the pathogenesis of CKD. This study aims to explore whether BM-MSC exerted anti-inflammatory effects in renal proximal tubular cells (PTEC) under milieu mimicking proteinuric nephropathy. METHODS: PTEC were treated with human albumin serum (HSA) and co-cultured with BM-MSC for 6 hours and 24 hours. Transcription and secretion of proinflammatory mediators were measured by real-time qPCR and ELISA, respectively. NF-κB signaling was assessed by western blot. RESULTS: Real-time qPCR revealed that co-culture with BM-MSC significantly reduced the up-regulated mRNA transcripts including IL6, CCL2, CCL5, IL8, TNF-alpha, IL1-beta, and ICAM-1 in PTEC exposed to HSA. The suppression of proinflammtory genes translated into reduced secretion of IL-6, CCL2, CCL5, IL8 and TNF-alpha proteins as detected by ELISA. In addition, the reduction of these proinflammtory cytokines and chemokines by BM-MSC was associated with attenuation of HSA induced I-κB phosphorylation in PTEC. To dissect the potential mechanism, we detected that the anti-inflammatory genes, HGF and IL1RN (IL1 receptor antagonist), were significantly induced in BM-MSC during co-culture with PTEC under protein overload condition. CONCLUSIONS: Our in vitro data suggest an anti-inflammatory role of BM-MSC in HSA-elicited PTEC inflammation, probably through paracrine effects of HGF and IL1RN via NF-κB signaling.