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 colon cancer are poorly understood. The observation that NSAIDs act as chemopreventative agents and reduce the size of colonic polyps suggests the involvement of inflammatory signalling, but inflammatory signalling in colonic polyps has not been studied. We investigated the expression of the active forms of NF-kappaB, JNK and p38 MAPK using immunohistochemistry with activation specific antibodies in human colonic adenomas. We show that active NF-kappaB is seen in stromal macrophages that also express COX-2 and TNF-alpha, active JNK is seen in stromal and intraepithelial T-lymphocytes and periendothelial cells of new blood vessels, and active p38 MAPK is most highly expressed in macrophages and other stromal cells. These results demonstrate the presence of active inflammatory signal transduction in colonic polyps and 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 evidence that NSAIDs may act through effects on stromal cells rather than epithelial cells.
Hardwick
J C
JC
Department of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
van den Brink
G R
GR
Offerhaus
G J
GJ
van Deventer
S J
SJ
Peppelenbosch
M P
MP
D018256:Adenomatous Polyps / Q000098:blood supply / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000737:chemistry*; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000302:isolation & purification; D048031:JNK Mitogen-Activated Protein Kinases; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000302:isolation & purification*; D016328:NF-kappa B / Q000302:isolation & purification*; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000302:isolation & purification; D048051:p38 Mitogen-Activated Protein Kinases
D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases