Insulin-like growth factor (IGF) induced proliferation of human lung fibroblasts is enhanced by neurotensin

Fibroblasts are key cells in tissue repair and important contributors to the inflammatory response. Insulin-like growth factors (IGFs) have been shown to participate in growth, in immune responses and in tissue repair where they stimulate cell growth. Neurotensin (NT) has been suggested to participate in inflammation and in tissue repair and is an autocrine or paracrine growth factor for several cancer cell types. Here we show that IGF-induced proliferation of fibroblasts is enhanced by NT in a concentration and type 1 NT-receptor dependent manner. This action of NT was blocked by inhibitors of phospholipase C and protein kinase C but not by inhibitors of phosphoinositide-3-kinase. An inhibitor of MEK 1/2 significantly reduced the proliferative effects of the IGFs but NT's ability to enhance IGF-induced proliferation was not effected. The ability of NT to enhance IGF-induced proliferation did not involve an autocrine factor. These results suggest that interactions between NT and the IGFs may contribute to the regulation of fibroblasts in for example, inflamed or injured tissues. (c) 2005 Elsevier Inc. All rights reserved.