Fibrogenic and inflammatory cytokines modulate mRNA expressions of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-3 in type II pneumocytes

Background: Imbalance between proteinases and their inhibitors released fro m alveolar type II pneumocytes may cause development of inflammatory lung d iseases. Objectives and Methods: We examined mRNA expressions of matrix met alloproteinase-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 rea ction. Results: Interleukin-1 beta (IL-1 beta) and transforming growth fact or-beta1 (TGF-beta1) increased MMP-3 and TIMP-3 expressions in A549 cells i n a time- and concentration-dependent manner. IL-1 beta mainly augmented MM P-3 expression, while TGF-beta1 mainly augmented TIMP-3 expression. Dexamet hasone attenuated both IL-1 beta- and TGF-beta1-stimulated expressions of M MP-3 and TIMP-3. Interleukin-10 had no significant effect. Hepatocyte growt h factor alone had no effect on constitutive MMP-3 expression or TIMP-3 exp ression, but it augmented TGF-beta1-stimulated MMP-3 expression. The consti tutive expressions were higher in normal type II pneumocytes than in A549 c ells, but the regulations were similar. Conclusions: These data indicated t hat the matrix degradation is enhanced by IL-1 beta and suppressed by TGF-b eta1 via regulations in the balance between MMP-3 and TIMP-3. Further, thes e regulations were shown to be modulated by glucocorticoids and growth fact ors. Copyright (C) 2001 S. Karger AG, Basel.