Macrophage migration inhibitory factor activates antigen-presenting dendritic cells and induces inflammatory cytokines in ulcerative colitis.
The 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 x 5 +/- 9 x 8 ng/ml, n = 10) compared with patients with Crohns disease (CD) (4 x 6 +/- 2 x 5 ng/ml, n = 5, P< 0 x 01) and control subjects (5 x 0 +/- 2 x 6 ng/ml, n = 10, P< 0 x 01). A double immunofluorescence study revealed the expression of MIF by CD83-positive mature DC at the colonic mucosa from UC patients. Blood DC treated with high amounts of MIF (500 ng/ml) showed a significantly higher stimulatory capacity (43287 +/- 5998 CPM, n = 5) in an allogenic mixed leucocyte reaction compared with untreated DC (27528 +/- 8823 CPM, n = 5, P< 0 x 05). Study of intracellular cytokine expression showed that MIF induced significant levels of interleukin (IL)-1 and IL-8 in monocytes and DC from UC and CD patients. These results showing the capacity of MIF to induce increased functional capacity of DC, and to produce IL-1 and IL-8 from monocytes and DC, indicate a role of MIF in the induction and/or perpetuation of the inflammatory environment in UC.
Third Department of Internal Medicine, Ehime University School of Medicine, Japan.
H
H
Murakami
S M F
SM
Akbar
H
H
Matsui
N
N
Horiike
M
M
Onji
D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology*; D003106:Colon / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha