ISS inhibits expression of MMP-9 and MMP-2 in a mouse model of airway remodeling

Abstract

Rationale MMPs are involved in the regulation of collagen deposition in the extracellular matrix. We investigated whether repetitive allergen challenge in mice induces expression of MMPs and TIMP-1 in the remodeled airway and whether ISS modulates expression of MMPs and TIMP-1. Methods Mice were repetitively challenged with OVA for 3 months to assess levels of MMP and TIMP expression (Elisa, immunohistochemistry). Levels of total lung collagen were measured by the Sircol soluble collagen assay. The effect of ISS on MMP and TIMP-1 expression was assessed by pretreating ova challenged mice with ISS every 2 weeks. Results Repetitive ova challenge induced a significant increase in the levels of lung MMP-9, MMP-2, and TIMP-1 (p=0.01). ISS treatment of ova challenged mice significantly reduced the levels of MMP-9,-2 and TIMP-1 compared to ova challenged mice not treated with ISS (p=0.01). Repetitive ova challenge induced a significant increase in the levels of lung collagen(p=0.01). ISS treatment of ova challenged mice significantly reduced the levels of lung collagen compared to ova challenged mice not treated with ISS (p=0.01, n=16). Conclusion Repetitive ova challenge induces increased levels of lung collagen which is associated with increased levels of expression of MMP-9, -2, and TIMP-1. ISS reduces lung collagen levels, as well as levels of MMP-9, -2 and TIMP-1, suggesting a role for ISS in inhibiting airway remodeling.