Cell cycle-dependent localization of tissue inhibitor of metalloproteinases-1 immunoreactivity in cultured human gingival fibroblasts.

Localization of the tissue inhibitor of metalloproteinases-1 (TIMP-1) was investigated in cultured human gingival fibroblasts by immunohistochemistry. TIMP-1 immunostaining was observed in the cytoplasm of a majority of cells, and in the nucleus of some cells. Depletion of fetal calf serum (FCS) from the culture medium reduced the density of immunoreactive TIMP-1 in the nucleus more remarkably than in the cytoplasm, and the following FCS-induced cell growth was accompanied by a recovery of immuno-reactive TIMP-1 in both the nucleus and the cytoplasm. The frequency of the nuclear TIMP-1-positive cells changed in line with that of PCNA-positive cells and was always much higher than that of S-phase cells, which were estimated by a pulse labelled 5-Bromo-2' deoxyuridine (BrdU). These results suggest a localization of TIMP-1 or a related substance in the nucleus of proliferating human fibroblasts, and its depletion from the nucleus due to an arrest of cell growth.