IL-5 production by bone marrow stromal cells: Implications for eosinophilia associated with asthma

Background: Eosinophil infiltration of bronchial tissue is a hallmark of as thma, Recruitment of eosinophils into pulmonary tissue is dependent on the presence of IL-5, In addition, IL-5 plays a significant role in the differe ntiation, proliferation, and maturation of eosinophil progenitor cells in t he bone marrow before recruitment into the lung. The contribution of bone m arrow eosinophil production to eosinophilia associated with asthma is poorl y understood. Objective: The aims of this study were to determine whether bone marrow str omal cells produce IL-5 and to determine whether IL-5 production by stromal cells is upregulated by IL-1, an inflammatory cytokine associated with ast hma, Methods: IL-5 messenger (m)RNA from bone marrow stromal cells was amplified by RT-PCR and sequenced. Stromal cells were lysed, and IL-5 protein produc tion was measured by ELISA, Upregulation of stromal cell IL-5 transcription , translation, and functional effect on eosinophil differentiation was eval uated after stimulation with recombinant IL-1 alpha and IL-1 beta and compa red with untreated cells. Results: Bone marrow stromal cells transcribe and translate IL-5. The nucle otide sequence of IL-5 mRNA from stromal cells was identical to that previo usly reported for murine T cells. IL-5 mRNA. abundance in stromal cells inc reased with increasing cell confluence in culture, IL-5 mRNA and protein le vels were upregulated by exposure of stromal cells to the inflammatory cyto kines IL-1 alpha and IL-1 beta, Exposure of stromal cells to IL-1 resulted in increased eosinophil differentiation in coculture experiments with nonad herent bone marrow cells. Conclusion: The production of IL-5 mRNA and protein by bone marrow stromal cells is a novel finding that has implications for both normal eosinophilop oiesis and development of the accelerated eosinophil production associated with asthma.