Abstract
Mesenchymal stem cells (MSCs) are pluri‐potent cells derived from the bone marrow that possess the capacity to regulate the cellular microenvironment by production of various cytokines, chemokines, and matrix proteins. The objective of this study was to identify novel products secreted by MSCs that may modulate the inflammatory response. Interrogation of the murine MSC transcriptome, which we previously catalogued via serial analysis of gene (SAGE), revealed numerous SAGE tags corresponding to interleukin 1 receptor antagonist (IL1RN). Screening of a murine MSC cDNA library by PCR confirmed that cells expressed mRNAs encoding IL1RN. Furthermore, fractionation studies indicated that MSCs are the principal source of IL1RN in murine bone marrow. FACS analysis further revealed that expression of IL1RN was restricted to ∼24% of murine MSCs, which was confirmed by immunostaining. Enzyme‐linked immunosorbent assays (ELISA) demonstrated that murine MSCs secrete approximately 3ng/ml/cell of IL1RN protein. Studies conducted in vitro showed that media conditioned by MSCs was able to block in a dose dependent fashion the ability of IL‐1α to stimulate proliferation of a T cell line. This inhibitory effect of MSC conditioned media could be abrogated by a neutralizing anti‐IL1RN antibody, thereby demonstrating that the effect was specific to IL1RN secreted by cells. Collectively, these studies identify a unique subpopulation of murine MSCs that express high levels of IL1RN, which functions to antagonize the activity of IL‐1α This activity may account, in part, for the anti‐inflammatory effects of MSCs in vivo.
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