interleukin-8 and 5-hydroxymethylcytosine

Mesenchymal stem/stromal cells (MSCs) possess some characteristics of immune cells, including a pro-inflammatory phenotype, an immunosuppressive phenotype, antibacterial properties and the expression of Toll-like receptor proteins. Here we show that, similar to immune cells, MSCs retain information from danger signals or environmental stimuli for a period of time. When treated with the pro-inflammatory factors lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α), MSCs display increased expression of IL-6, IL-8 and MCP-1. Following re-plating and several rounds of cell division in the absence of stimulating factors, the expression of IL-6, IL-8 and MCP-1 remained higher than in untreated cells for over 7 days. A spike in cytokine secretion occurred when cells were exposed to a second round of stimulation. We primed MSCs with LPS and LPS-primed MSCs had better therapeutic efficacy at promoting skin flap survival in a diabetic rat model than did unprimed MSCs. Finally, we found that several microRNAs, including miR146a, miR150 and miR155, along with the modification of DNA by 5-hydroxymethylcytosine (5hmC), mediate the MSC response to LPS and TNF-α stimulation. Collectively, our data suggest that MSCs have a short-term memory of environmental signals, which may impact their therapeutic potential.

Topics: 5-Methylcytosine; Adipose Tissue; Animals; Cell Differentiation; Cell Proliferation; Cell Shape; Chemokine CCL2; Diabetes Mellitus, Experimental; DNA Methylation; Enzyme-Linked Immunosorbent Assay; Immunologic Memory; Immunophenotyping; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; MicroRNAs; Rats, Wistar; Real-Time Polymerase Chain Reaction; Signal Transduction; Surgical Flaps; Tissue Survival; Tumor Necrosis Factor-alpha