CYTOKINE-MEDIATED REGULATION OF TYPE-IV COLLAGENASE EXPRESSION AND PRODUCTION IN HUMAN TROPHOBLAST CELLS

The invasive property of trophoblast cells is dependent on the activit y of proteolytic enzymes of the metallo- and serine proteases family. Interleukin-l (IL-l) was found to be involved in the regulation of the se proteases in various systems, serving as an important modulator in trophoblast physiology (e.g. induction of hCG beta, cytokines, and oth ers). Therefore, consideration is given in this report to the role of IL-1 in the regulation of metalloprotease activity in human trophoblas ts. Human trophoblast cells were isolated from first trimester placent as by trypsin degradation and Percoll fractionation. Primary cell cult ures of first trimester trophoblasts constitutively elaborated two spe cies of collagenase type IV (92 and 72 kDa), as assessed in gelatin ma trix. Treatment with IL-1 further augmented the 92-kDa type IV collage nase secretion in a dose-dependent manner. Furthermore, IL-1 significa ntly (P <0.01) increased 92-kDa collagenase gene expression by trophob last cells, as determined by solution hybridization/ribonuclease prote ction assay. Both the increase in gene expression and protein biosynth esis of the 92-kDa collagenase type IV were neutralized by the soluble IL-1 receptor, indirectly suggesting a receptor-mediated response. In terestingly, transforming growth factor-beta a putative modulator of I L-1-induced effects, was shown to induce the 92-kDa collagenase type I V secretion as well. These results provide indirect evidence supportin g the idea that IL-1 and transforming growth factor-beta may play an i ntermediary role in trophoblast invasion at the fete-maternal interfac e by regulating trophoblast expression of 92-kDa type IV collagenase, a protease of prime importance in trophoblast invasion.