Cell-matrix interactions modulate 92-kD gelatinase expression by human bronchial epithelial cells.

Abstract

We have previously reported that primary human bronchial epithelial cells (HBECs) cultured on types I + III collagen were able to differentially regulate the production of major constitutive 92-kD gelatinase, minor 72-kD gelatinase, and their tissue-specific inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) in response to lipopolysaccharide (LPS) or proinflammatory cytokines, suggesting that HBECs may be involved in vivo in the active remodeling of the underlying extracellular matrix (ECM). In this study, we examined the possible effects of specific type IV collagen as compared with types I + III collagen on HBEC behavior and function. We investigated 92-kD gelatinase and TIMP-1 expression 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 morphologic features and identical proliferation rates of HBECs in response to the two matrix substrates. Nevertheless, differences at the protein and mRNA levels between HBEC cultures on type IV collagen and on types I + III collagen included: (1) a lower basal level of 92-kD gelatinase production; (2) less upregulation of 92-kD gelatinase in response to LPS endotoxin or to the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha); and (3) loss of activation of the proforms of the 92-kD and 72-kD gelatinases. These findings, together with the maintenance of TIMP-1 expression, strongly suggest that type IV collagen used as a matrix substratum is associated with a homeostatic HBEC phenotype, and limits the ability of HBECs 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 modulate matrix remodeling by HBECs, particularly in response to inflammatory processes during acute lung injury.