INTERLEUKIN-1-ALPHA STIMULATES NUCLEAR PHOSPHOLIPASE-C IN HUMAN OSTEOSARCOMA SAOS-2 CELLS

Interleukin 1 (IL-1) is one of the most potent stimulators of bone res orption. However, the early biochemical events elicited by IL-1 recept or binding are not fully understood. Here we show that in human osteos arcoma SaOS-2 cells the treatment with IL-1alpha is able to evoke a ra pid and transient increase of nuclear phospholipase C (PLC) activity. A parallel decrease of nuclear phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate is observed. All these events are st rictly confined to the nuclear compartment without affecting the cytop lasmatic inositol lipid pool. In addition we show that by Western blot analysis with specific monoclonal antibodies the PLC gamma is located both in the cytoplasm and in the nucleus, while PLC beta appears excl usively Iocalized in the nucleus. Moreover, the increase of PLC activi ty in response to IL-1alpha is completely neutralized by monoclonal an tibody against the beta-form. While confirming the existence of an aut onomous nuclear phosphoinositide signaling system, our data clearly in dicate that in SaOS-2 cells one of the earliest events following IL-1a lpha treatment is the breakdown of nuclear phosphatidylinositol monoph osphate and phosphatidylinositol bisphosphate because of the activatio n of a specific nuclear PLC isoform.