The expression of LEC/CCL16, a powerful inflammatory chemokine, is upregulated in ulcerative colitis.
Ulcerative colitis (UC) is a chronic inflammatory disease of unknown aetiology and pathogenesis. The presence in the colonic mucosa of reactive cells expressing proinflammatory cytokines and chemokines is associated with high levels of IL-10, an anti-inflammatory cytokine. Our aim was to investigate the role of IL-10 and the beta chemokine LEC/CCL16 selectively up-regulated by IL-10 in inflammatory cell recruitment and cytokine and chemokine production during UC. We studied histologically, immunohistochemically and ultrastructurally colonic biopsies from 20 active UC patients and 10 control specimens taken far from any macroscopically detectable lesion in age and sex-matched patients with noninflammatory bowel disease. In active UC, immature dendritic cells (DCs) in the LP are associated with IL-10 in the T cell rich area. Furthermore, most of the LP-infiltrating macrophages strongly expressed LEC/CCL16, a chemokine upregulated by IL-10. To evaluate if LEC/CCL16 plays a role in the inflammatory reaction present in UC, we performed morphological studies in mice injected s.c. with syngeneic tumor cells engineered to produce LEC/CCL16. We found that the LEC protein locally released by LEC-gene-transfected tumor cells is a potent proinflammatory chemokine that induces the recruitment of a reactive infiltrate, and an angiogenic process mirroring that in human UC.
Pannellini
T
T
Ce.S.I. G. d'Annunzio University Foundation, University of Chieti, Italy.
Iezzi
M
M
Di Carlo
E
E
Eleuterio
E
E
Coletti
A
A
Modesti
A
A
Rosini
S
S
Neri
M
M
Musiani
P
P
D000818:Animals; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D019742:Chemokines, CC / Q000096:biosynthesis*; D002999:Clone Cells; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000096:biosynthesis; D014162:Transfection; D015854:Up-Regulation / Q000502:physiology
D019742:Chemokines, CC; D012333:RNA, Messenger; D016753:Interleukin-10