Role of HSP70i in regulation of biomaterial-induced activation of human monocytes-derived macrophages in culture.

The functioning of an implant depends on the material properties and the wound-healing process. The latter is led by an inflammatory reaction guided mainly by monocyte/macrophage activity. This in vitro study investigated human monocytes/macrophages in culture from 2 h to 10 days on silicone, polyurethane, teflon and TCPS. Analysis of cytokine release by ELISA showed that maturing macrophages have different capacities to produce cytokines TNFalpha, IL10, IL8 and GM-CSF. The long culture-mature macrophages on all polymers produced comparable low levels of TNFalpha, IL10 and IL8. Monocytes/macrophages on polyurethane and teflon, and those on silicone only in long culture-time produced high GM-CSF amounts, where as those on TCPS exhibited low levels of GM-CSF. FACS analysis revealed that HSP70i was highly inducible after short time culture yet this high level was maintained in long culture-mature macrophages on TCPS only, whereas on other polymers the mature macrophages showed a high reduction in HSP70i level, which demonstrated a high stress-response by cells on TCPS. Accordingly, CLSM-analysis revealed low nuclear NF-kappaB in cells on TCPS and high nuclear NF-kappaB in mature macrophages on silicone and polyurethane, showing a high cellular activation on the latter two polymers. This corresponded also to the high mitochondrial activity by XTT metabolism displayed by the mature macrophages on polyurethane >/= silicone > teflon > TCPS. These data show a correlation of (1) cytokines (TNFalpha, GM-CSF) and HSP70i, (2) NF-kappaB and HSP70i by monocytes/macrophages after contact with polymers. Thus, HSP70i might be a useful molecular candidate for exploring biomaterial-induced inflammatory reaction.