Mechanisms of allergy and clinical immunologyMatrix metalloproteinase 8 contributes to solubilization of IL-13 receptor α2 in vivo
Section snippets
Animals
Animals were maintained and handled under institutional animal care and use committee–approved procedures. C57BL/6 MMP-8–deficient mice were kindly provided by Dr Steven D. Shapiro (University of Pittsburgh School of Medicine, Pittsburgh, Pa),31 and the wild-type C57BL/6 and FVB/N mice were purchased from Jackson Laboratories (Bar Harbor, Me). HDM (Dermatophagoides pteronyssinus) was purchased from Greer Laboratories (Lenoir, NC). The mice were immunized as previously described.21 Two days
Increased levels of soluble IL-13Rα2 in serum and BALF and MMP expression in lungs in a murine model of asthma
We characterized soluble IL-13Rα2 levels in the serum and BALF in mice sensitized and challenged with HDM. As shown in Fig 1, A and B, the level of soluble IL-13Rα2 was increased in both serum and BALF in HDM-treated mice compared with that seen in PBS-treated mice. To determine the expression of different MMPs in the murine lungs after HDM sensitization and challenge, we performed an RNase protection assay to examine mRNA expression for murine MMPs. As shown in Fig 1, C, HDM sensitization and
Discussion
Soluble cytokine receptors have important roles in the regulation of cell-signaling pathways.37, 38, 39 Shedding of membrane-bound receptors has been shown as a mechanism to generate soluble receptors.24, 25 In this article we demonstrated that soluble IL-13Rα2 can be produced by means of direct cleavage by MMP-8 and that MMP-8 contributes to the solubilization of IL-13Rα2 in BALF in HDM-treated mice.
MMPs have been shown to be important mediators of airway inflammation and remodeling.40 Among
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Supported by National Institutes of Health grant R01 AI58157 (G.K.K.H.).
Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.