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

Abstract

Background: Eosinophil infiltration of bronchial tissue is a hallmark of asthma. Recruitment of eosinophils into pulmonary tissue is dependent on the presence of IL-5. In addition, IL-5 plays a significant role in the differentiation, proliferation, and maturation of eosinophil progenitor cells in the bone marrow before recruitment into the lung. The contribution of bone marrow eosinophil production to eosinophilia associated with asthma is poorly understood. Objective: The aims of this study were to determine whether bone marrow stromal cells produce IL-5 and to determine whether IL-5 production by stromal cells is upregulated by IL-1, an inflammatory cytokine associated with asthma. 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 production was measured by ELISA. Upregulation of stromal cell IL-5 transcription, translation, and functional effect on eosinophil differentiation was evaluated after stimulation with recombinant IL-1α and IL-1β and compared with untreated cells. Results: Bone marrow stromal cells transcribe and translate IL-5. The nucleotide sequence of IL-5 mRNA from stromal cells was identical to that previously reported for murine T cells. IL-5 mRNA abundance in stromal cells increased with increasing cell confluence in culture. IL-5 mRNA and protein levels were upregulated by exposure of stromal cells to the inflammatory cytokines IL-1α and IL-1β. Exposure of stromal cells to IL-1 resulted in increased eosinophil differentiation in coculture experiments with nonadherent 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 eosinophilopoiesis and development of the accelerated eosinophil production associated with asthma. (J Allergy Clin Immunol 2000;106:329-36.)