TGF-β1 production in inflammatory bowel disease: differing production patterns in Crohn's disease and ulcerative colitis

Autor: G. Mumolo, Roberto Tersigni, B. Del Zotto, Chiara Montesani, Monica Boirivant, Annamaria Pronio
Jazyk: angličtina
Rok vydání: 2003
Předmět:
Popis: SUMMARY Transforming growth factor-β (TGF-β) is an inhibitory cytokine recognized as a key regulator of immunological homeostasis and inflammatory responses. TGF-β is involved in experimental models of oral tolerance and in the pathogenesis of experimental colitis. Patients with inflammatory bowel disease (IBD) have inappropriate T cell responses to antigenic components of their own intestinal microflora, suggesting the presence of a disorder in the normal mucosal immune mechanism that ensures the down-regulation of responses to harmless constituents in the microflora. To evaluate the contribution of TGF-β to this imbalance, we measured TGF-β1 production by lamina propria mononuclear cells (LPMC) and T cells isolated from tissue specimens of patients with Crohn's disease (CD), ulcerative colitis (UC) and controls. Cells were cultured in the presence or absence of anti-CD2 plus anti-CD28 MoAbs and TGF-β1 production in culture supernatants was measured by ELISA. LPMC isolated from CD patients produced significantly less TGF-β1 than controls when stimulated via CD2 plus CD28 pathways (P = 0·001)] conversely, in UC patients increased production of TGF-β1 compared to controls was observed (P = 0·0005). These differences were also observed with purified lamina propria (LP) T cells in both diseases and were associated with the presence of inflammation. Thus, TGF-β1 production shows contrasting secretion in CD and in UC, probably as a consequence of the different Th polarization. The absolute or relative defect in TGF-β1 production observed in CD and UC may contribute to the perpetuation of inflammation.
Databáze: OpenAIRE