Central role of IL-6 and MMP-1 for cross talk between human intestinal mast cells and human intestinal fibroblasts

Mast cells (MC) are key effector cells in allergic reactions but also involved in host defence, tissue remodeling, angiogenesis, and fibrogenesis. Here, we show that human intestinal fibroblasts (FB) suppress apoptosis in human intestinal MC dependent on IL-6. Intestinal FB produced IL-6 upon direct stimulation by intestinal MC in co-culture or by MC mediators such as TNF-α, IL-1β, tryptase or histamine. MC incubated with IL-6 survived for up to 3 weeks similar to MC co-cultured with FB and MC survival could be blocked by neutralizing anti-IL-6 Abs. Moreover, FB stimulated by MC mediators upregulated their expression of matrix metalloproteinase-1 (MMP-1), a key fibrolytic enzyme. Noteworthy, FB co-cultured with MC or treated with MMP-1 lost confluence and showed increased numbers of apoptotic cells. Our data indicate an intimate cross talk between mucosal MC and FB resulting in MC survival and induction of a fibrolytic rather than a profibrotic state in FB.