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 from alveolar type II pneumocytes may cause development of inflammatory lung diseases.


OBJECTIVE
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-1beta (IL-1beta) and transforming growth factor-beta1 (TGF-beta1) increased MMP-3 and TIMP-3 expressions in A549 cells in a time- and concentration-dependent manner. IL-1beta mainly augmented MMP-3 expression, while TGF-beta1 mainly augmented TIMP-3 expression. Dexamethasone attenuated both IL-1beta- and TGF-beta1-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-beta1-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-1beta and suppressed by TGF-beta1 via regulations in the balance between MMP-3 and TIMP-3. Further, these regulations were shown to be modulated by glucocorticoids and growth factors.
Hoshino
Y
Y
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. yuma@kuhp.kyoto-u.ac.jp
Mio
T
T
Nagai
S
S
Ito
I
I
Shigematsu
M
M
Izumi
T
T
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008168:Lung / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D019278:Matrix Metalloproteinase 3 / Q000187:drug effects* / Q000235:genetics*; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects* / Q000502:physiology*; D012016:Reference Values; D013997:Time Factors; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000187:drug effects* / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3; D016212:Transforming Growth Factor beta; D019278:Matrix Metalloproteinase 3