Fibrogenic and Inflammatory Cytokines Modulate mRNA Expressions of Matrix Metalloproteinase-3 and Tissue Inhibitor of Metalloproteinase-3 in Type II Pneumocytes

Abstract

Background: Imbalance between proteinases and their inhibitors released from alveolar type II pneumocytes may cause development of inflammatory lung diseases. Objectives and Methods: We examined mRNA expressions of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-3 (TIMP-3) in a cell line (A549) and in primary culture of normal adult human type II pneumocytes using reverse transcription-competitive polymerase chain reaction. Results: Interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) increased MMP-3 and TIMP-3 expressions in A549 cells in a time- and concentration-dependent manner. IL-1β mainly augmented MMP-3 expression, while TGF-β1 mainly augmented TIMP-3 expression. Dexamethasone attenuated both IL-1β- and TGF-β1-stimulated expressions of MMP-3 and TIMP-3. Interleukin-10 had no significant effect. Hepatocyte growth factor alone had no effect on constitutive MMP-3 expression or TIMP-3 expression, but it augmented TGF-β1-stimulated MMP-3 expression. The constitutive expressions were higher in normal type II pneumocytes than in A549 cells, but the regulations were similar. Conclusions: These data indicated that the matrix degradation is enhanced by IL-1β and suppressed by TGF-β1 via regulations in the balance between MMP-3 and TIMP-3. Further, these regulations were shown to be modulated by glucocorticoids and growth factors.