Pm. Yao et al., CELL-MATRIX INTERACTIONS MODULATE 92-KD GELATINASE EXPRESSION BY HUMAN BRONCHIAL EPITHELIAL-CELLS, American journal of respiratory cell and molecular biology, 18(6), 1998, pp. 813-822
We have previously reported that primary human bronchial epithelial ce
lls (HBECs) cultured on types I + III collagen were able to differenti
ally regulate the production of major constitutive 92-kD gelatinase, m
inor 72-kD gelatinase, and their tissue-specific inhibitor, tissue inh
ibitor of metalloproteinase-1 (TIMP-1) in response to lipopolysacchari
de (LPS) or proinflammatory cytokines, suggesting that HBECs may be in
volved in vivo in the active remodeling of the underlying extracellula
r matrix (ECM). In this study, we examined the possible effects of spe
cific type IV collagen as compared with types I + III collagen on HBEC
behavior and function. We investigated 92-kD gelatinase and TIMP-1 ex
pression with zymography and reverse zymography, respectively, at the
protein level, and with quantitative reverse transcription-polymerase
chain reaction (RT-PCR) at the mRNA level. Results showed similar morp
hologic features and identical proliferation rates of HBECs in respons
e to the two matrix substrates. Nevertheless, differences at the prote
in and mRNA levels between HBEC cultures on type IV collagen and on ty
pes I + III collagen included: (1) a lower basal level of 92-kD gelati
nase production; (2) less upregulation of 92-kD gelatinase in response
to LPS endotoxin or to the proinflammatory cytokines interleukin-1 be
ta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha); and (3) lo
ss of activation of the proforms of the 92-kD and 72-kD gelatinases. T
hese findings, together with the maintenance of TIMP-1 expression, str
ongly suggest that type IV collagen used as a matrix substratum is ass
ociated with a homeostatic HBEC phenotype, and limits the ability of H
BECs to degrade the matrix. In contrast, types I + III collagen may be
associated with a matrix resorption phenotype corresponding to active
matrix remodeling and repair. Thus, the ECM underlying HBECs may modu
late matrix remodeling by HBECs, particularly ih response to inflammat
ory processes during acute lung injury.