NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps

The factors that govern the progression from colonic adenomatous polyp to c olon cancer are poorly understood. The observation that NSAIDs act as chemo preventative agents and reduce the size of colonic polyps suggests the invo lvement of inflammatory signalling, but inflammatory signalling in colonic polyps has not been studied. We investigated the expression of the active f orms of NF-kappaB, JNK and p38 MAPK using immunohistochemistry with activat ion specific antibodies in human colonic adenomas, We show that active NF-k appaB is seen in stromal macrophages that also express COX-2 and TNF-alpha, active JNK is seen in stromal and intraepithelial T-lymphocytes and perien dothelial cells of new blood vessels, and active p38 MAPK is most highly ex pressed in macrophages and other stromal cells. These results demonstrate t he presence of active inflammatory signal transduction in colonic polyps an d that these are predominantly in the stroma, In the case of NF-kappaB this coincides with the cellular localisation of COX-2. These results support e vidence that NSAIDs may act through effects on stromal cells rather than ep ithelial cells.