SUMMARYPatients with chronic hepatitis C (CHC) are unable to prime and maintain vigorous T cell responses that are initiated during the acute phase of hepatitis C virus (HCV) infection. As dendritic cells (DCs) induce and regulate both innate and adaptive immune responses, the aim of this study was to analyse two critical functions of DCs: firstly, production of interferon (IFN)-a and, secondly, polarization of T helper 1 lymphocytes. The frequencies of plasmacytoid DC (PDC) and myeloid DC (MDC) were estimated in 63 patients with CHC and 34 normal controls using four-colour flow cytometry. Circulating DCs were isolated from peripheral blood of CHC patients ( n = 10) and normal controls ( n = 10). These DCs were cultured with herpes simplex virus-1 to evaluate their capacity to produce IFN-a . The capacity of DCs to induce polarization of autologous naive CD4 + T lymphocytes to IFN-g -producing effector T lymphocytes was also assessed. The frequencies of PDCs producing intracellular IFN-a ( P < 0·01) and the levels of IFN-a in culture supernatant of PDCs ( P < 0·01) were significantly lower in patients with CHC compared to those of normal controls. The numbers of MDC were significantly lower in patients with CHC (8·2 (6·0)/ m l, median (interquartile range), n = 63) compared to normal control (11·7 (7·8)/ m l, n = 34) ( P < 0·01). Moreover, DCs from patients with CHC induced significantly lower numbers of IFNg -producing effector T lymphocytes compared to that of controls ( P < 0·01). This study indicates that the low IFN-a -producing capacity and impaired T helper 1 polarization ability of DCs from patients with CHC might be responsible for the typical low anti-HCV immune responses in these patients.
These data suggest a role of MIF in the pathogenesis of UC. MIF may be used as a marker of disease activity in UC and control of MIF production may have therapeutic implications.
Both the motilin and ghrelin receptors are expressed along the human gastrointestinal tract, but they have clearly distinct distributions in regard to both level and layer. The diffuse muscle expression of the motilin receptor, at both the levels of the gene and the protein product, along the entire gastrointestinal tract makes it a useful potential target for motilide drugs for dysmotility.
Ulcerative colitis (UC) is an inflammatory disease of the colonic mucosa and seems to result from a complex series of interactions among susceptibility genes, the environment and the immune system [1,2]. Genetically-susceptible individuals, or persons with an alteration of the mucosal immune system towards luminal antigens, are prone to develop UC. However, the final assault for initiation and/or perpetuation of this disease mainly comes from inflammatory cytokines such as tumour necrosis factor (TNF)-a and interleukin (IL)-1b, . These proinflammatory cytokines are produced mainly by activated lymphocytes and macrophages. However, little is known about the cellular events that lead to activation and recruitment of these cells in UC. As the antigen-presenting dendritic cells (DC) activate the lymphocytes and ensure the survival and functioning of activated lymphocytes [6,7], and macrophage migration inhibitory factor (MIF) inhibits the random migration of macrophages in vitro and promote macrophage accumulation in vivo [8], we conducted two separate experiments to study the role of DC and MIF, if any, in the pathogenesis of UC. The results showed that the functional capacity of peripheral blood DC and the numbers of mature and activated DC at the colonic mucosa were significantly increased in patients with UC compared with normal healthy controls and patients with ischemic and inflammatory colitis [9]. We further showed that the levels of MIF in the sera were significantly increased in patients with UC, and MIF-expressing cells were detected at the colonic mucosa in UC [10]. Although these studies indicate that activated DC and increased levels of MIF may be related to the pathogenesis of UC, a functional relationship between DC and MIF, and the role of MIF in the induction of inflammatory cytokines in UC, has not been studied.In the present experiments, we first studied the production of MIF by pure population of peripheral blood DC. We also checked the expression of MIF by DC at the colonic mucosa from UC patients and control subjects by double immunofluorescence methodology. Next, we evaluated the impact of MIF on the function of DC. Finally, the capacity of MIF to induce proinflammatory cytokines in T lymphocytes, monocytes and DC from normal subjects, UC and CD patients was assessed. 504 Macrophage migration inhibitory factor activates antigen-presenting dendritic cells and induces inflammatory cytokines in ulcerative colitis SUMMARYThe level of macrophage migration inhibitory factor (MIF) and the functions of dendritic cells (DC) are up-regulated in the peripheral blood, and the numbers of MIF-expressing cells and mature DC are increased at the colonic mucosa from patients with ulcerative colitis (UC). However, a functional relationship between MIF and DC, and the role of MIF in the pathogenesis of UC, are not clear. In this study, we showed that a pure population of peripheral blood DC is a new and still unknown source of MIF. DC from UC patients produced significantly higher levels of MIF (17·5 ± 9·8 ng/...
Recently, the number of patients diagnosed with WD has been increasing, not only in terms of those with classical-type WD but also in terms of elderly patients or patients with non-cirrhotic liver injury such as fatty liver and chronic hepatitis. The various clinical features of WD should be recognized and particular attention should focus on HCC as a complication.
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