Biochemical and Biophysical Research Communications
Salmon cartilage proteoglycan suppresses mouse experimental colitis through induction of Foxp3+ regulatory T cells
Research highlights
► Salmon proteoglycan suppresses IL-10−/− cell transfer-induced colitis progression. ► Salmon proteoglycan suppresses Th1- and Th17-related factors in colitis mice. ► Salmon proteoglycan enhances Foxp3 expression.
Introduction
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is characterized by chronic inflammation of the gastrointestinal tract [1]. Inflammatory cytokines play an important role in the progression of IBD. CD has historically been considered a T-helper 1 (Th1)-mediated disease [2]. IL-12 is a key mediator in Th1 cell differentiation because of induction of IFN-γ in IBD [3]. In gut mucosa from patients with CD and UC, Th17 cells were detected and IL-17 was induced [4]. Lamina propria mononuclear cells (LPMCs) play a key role in mucosal immunity. Defective regulatory properties of regulatory T cells (Tregs) in LPMCs could contribute to the disturbed immune balance in IBD [5]. As a counterpart of cell lineage that promotes inflammation, Tregs can suppress inflammatory responses in IBD [6]. In rodents and humans, Tregs suppress proliferation and cytokine production of effector T cells [7].
Proteoglycans (PGs) are complex glycohydrates, which are composed of core proteins and glycosaminoglycans that bind to core proteins. PGs are involved in cellular proliferation and adhesion cooperated with collagen, fibronectin, and laminin [8]. Additionally, our previous study showed that PG suppresses inflammatory response of macrophages induced by stimulation with heat-killed bacteria [9]. In this study, we investigated whether administration of PG suppresses the progression of colitis. We show that PG attenuated the severity of colitis via induction of Tregs in vivo.
Section snippets
Mice
IL-10−/− mice on a C57BL/6 background were purchased from Jackson Laboratory, Bar Harbor, ME. CB-17/Icr severe combined immunodeficiency (SCID) mice were obtained from Clea Japan, Tokyo, Japan. SCID and IL-10−/− mice were bred under specific-pathogen-free conditions in the Institute for Animal Experimentations, Hirosaki University Graduate School of Medicine. All the animal experiments in this study were carried out in accordance with the guidelines for animal experimentation of Hirosaki
PG attenuated the severity of colitis
We investigated whether PG could affect colitis in mice. Colitis was induced by transfer of spleen cells and MLN cells from IL-10−/− mice and daily oral administration of various doses of PG was started simultaneously. Body weight of colitis-induced mice was measured once a week (Fig. 1A). Daily oral administration with PG attenuated body weight loss in colitis-induced mice in a dose-dependent manner (Fig. 1A). Then we observed the macroscopic appearance of colon (Fig. 1B), and colon weight was
Discussion
IBD is a chronic relapsing idiopathic inflammation of the gastrointestinal tract. IBD patients show dense infiltration of lymphocytes, fissuring ulceration, crypt abscesses and loss of goblet cells in colon [15]. In this study, we investigated the effect of PG extracted from salmon cartilage on the progression of experimental colitis that exhibits chronic inflammation induced by cell transfer from IL-10−/− mice. Enterocolitis was spontaneously developed in these animals [16]. The result showed
Acknowledgments
This research was supported by the City Area Program for Promotion of Science and Technology in Regional Areas from Ministry of Education, Culture, Sports, Science and Technology. This study was also supported by Grant for Hirosaki University Institutional Research.
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