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Ontsuka K.,Saga Medical School | Kotobuki Y.,Osaka University | Kotobuki Y.,National Institute of Biochemical Innovation | Shiraishi H.,Saga Medical School | And 15 more authors.
Experimental Dermatology | Year: 2012

Cutaneous wound repair is a highly ordered and well-coordinated process involving various cell lineages and many molecular effectors. Cell-matrix interactions through integrin molecules provide key signals important for wound repair. Periostin is a matricellular protein that may provide signals important during tissue development and remodelling by interacting with several integrin molecules, via the phosphatidylinositol 3-kinase/Akt and MAP kinase pathways. In this study, we examined the role of periostin in the process of cutaneous wound repair using periostin-deficient mice and by analysing the effects of periostin on dermal fibroblasts. We first determined the expression profile and localization of periostin in a well-characterized wound repair model mice. Periostin was robustly deposited in the granulation tissues beneath the extended epidermal wound edges and at the dermal-epidermal junctions in wounded mice. Moreover, periostin-deficient mice exhibited delayed in vivo wound repair, which could be improved by direct administration of exogenous periostin. In vitro analyses revealed that loss of periostin impaired proliferation and migration of dermal fibroblasts, but exogenous supplementation or enforced periostin expression enhanced their proliferation. Combined, these results demonstrate that periostin accelerates the process of cutaneous wound repair by activating fibroblasts. © 2012 John Wiley & Sons A/S.

Hohki S.,Osaka University | Ohguro N.,Osaka University | Haruta H.,Osaka University | Nakai K.,Osaka University | And 7 more authors.
Experimental Eye Research | Year: 2010

The aim of this study was to investigate the effect of anti-mouse IL-6 receptor monoclonal antibody (MR16-1) treatment on CD4 T cell differentiation and compared it to the effect of anti-TNF mAb treatment with using a murine model of experimental autoimmune uveoretinitis (EAU). C57BL/6 mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) to induce ocular inflammation treatment with control IgG or MR16-1 or anti-TNF mAb. Helper T cells differentiation was analyzed during the development of EAU. Immunization with IRBP increased the frequency of Th17 cells rather than Th1 cells in the early stage of EAU. Treatment with MR16-1 on the same day as immunization (day 0) or one day after (day 1) suppressed ocular inflammation in EAU mice. Treatment with MR16-1 on day 0 inhibited the induction of Th17 cells in vivo, and inhibited not only IRBP-responsive Th17 cells but also their Th1 counterparts and induced IRBP-responsive regulatory T (Treg) cells in vitro. The administration of anti-TNF mAb had no significant protective effect in EAU mice. The protective effect of anti-IL-6R mAb treatment, but not anti-TNF mAb treatment on EAU correlated with the inhibition of Th17 differentiation. This finding suggests that IL-6 blockade may have a therapeutic effect on human ocular inflammation which is mediated via mechanisms distinct from those of TNF blockade. IL-6 blockade may thus represent an alternative therapy for patients with ocular inflammation who are refractory to anti-TNF mAb therapy. © 2010 Elsevier Ltd.

Kiyohara H.,Kitasato University | Uchida T.,Kitasato University | Takakiwa M.,Kitasato University | Matsuzaki T.,Kitasato University | And 4 more authors.
Phytochemistry | Year: 2010

Thirteen polysaccharides isolated from an extract of the aerial portions of Astragalus mongholics Bunge demonstrated immunomodulating activity against Peyer's patch immunocompetent cells. Nine of the active polysaccharide fractions were composed of either arabinogalactans, pectic arabinogalactans or pectins. The activities of the arabinogalactans and pectic arabinogalactans were associated with β-d-(1 → 3)-galactan moieties branched with β-d-(1 → 6)-galactooligosaccharide side-chains having degrees of polymerization of 8 or less. Degradation of the β-d-(1 → 3)-galactan or β-d-(1 → 6)-galactosyl side-chains in the arabinogalactans significantly decreased immunomodulating activity. Rhamnogalacturonan I (RG-I) with β-d-(1 → 3,6)-galactosyl side-chains having terminal β-d-GlcA showed activity in the pectin-enriched fractions. Interestingly, the terminal GlcA was not required for activity of the arabinogalactan-enriched fractions, suggesting at least two different immunomodulating structures. © 2009 Elsevier Ltd. All rights reserved.

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