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Atsuko Yoneda Athanassios Dovas Hinke A.B. Multhaupt John R. Couchman 《International journal of experimental pathology》2004,85(1):A25-A25
Introduction The transmembrane heparan sulfate proteoglycan, syndecan‐4, and integrins are important receptors for focal adhesion (FA) formation on fibronectin (FN) substrates. The small GTPase RhoA is also known to regulate FA and stress fiber formation. It has been suggested that syndecan‐4 and integrins co‐operatively regulate the assembly of FA in a Rho‐dependent manner, but the mechanism is unclear. Here, we examined the function of RhoA and the Rho effector kinases ROCKs in syndecan‐4 signalling on the process of FA formation and the possible mechanism by which syndecan‐4 may regulate RhoA activity. Methods Primary rat embryonic fibroblasts (REFs) were seeded on FN or ‘RGD’‐containing integrin‐binding domain of FN and lysed at various time points. The amount of active form of RhoA in each lysate was analysed by pull‐down experiments. Results and discussion The relative activities of RhoA showed one peak in the process of FA formation on FN, whereas no peak was obtained on the integrin‐binding domain. The one peak of RhoA activity on integrin‐binding domain was restored by addition of heparin‐binding domain into medium. These results suggested that a signal through syndecan‐4 link to the Rho pathway. Both ROCK‐I and ‐II isozymes were present in REF cell lysates and each could be specifically immunoprecipitated. The ROCK kinase activities in immunoprecipitates were analysed using GST‐myosin light chain as a substrate. The amount of ROCK‐I and ‐II activities changed through the adhesion process on FN and appeared to be independently regulated. Therefore, one or both ROCKs may be downstream of a syndecan‐4‐mediated signalling response through RhoA. The core protein of syndecan‐4 can directly bind to and activate PKC‐α. We found that PKC‐α could phosphorylate Rho‐Guanine Nucleotide Dissociation Inhibitor (GDI) in vitro. It has been suggested that PKC‐α‐mediated phosphorylation of Rho GDI stimulates GDI dissociation, thereby resulting in Rho activation. It is possible that syndecan‐4 regulates Rho/ROCK pathway through PKC‐α activation on the process of FA formation. 相似文献
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Impact of intranasal budesonide on immune inflammatory responses and epithelial remodeling in chronic upper airway inflammation 总被引:3,自引:0,他引:3
Mastruzzo C Greco LR Nakano K Nakano A Palermo F Pistorio MP Salinaro ET Jordana M Dolovich J Crimi DN Vancheri C 《The Journal of allergy and clinical immunology》2003,112(1):37-44
BACKGROUND: Histologic and immunohistologic features of nasal polyps (NP) are similar to those observed in asthma, thus suggesting a similar immunopathology. OBJECTIVE: The primary objective of this study was to further understand the anti-inflammatory and immunoregulatory effects of locally delivered corticosteroids. To this end, the effect of intranasal budesonide on the expression of specific cytokines, lymphocyte subsets, and epithelial remodeling in this model of airway tissue inflammation were studied. METHODS: We used immunohistochemical techniques to examine nasal mucosae (NM) from healthy individuals and nasal polyp (NP) tissues from patients with nasal polyposis obtained before and after intranasal budesonide treatment. RESULTS: First, the density of CD8(+) cells was markedly increased in NP tissues after intranasal budesonide treatment from 16.1 +/- 8.4 (M +/- SEM) per mm(2) to 39.9 +/- 24.1. Second, the density of cells immunoreactive for IL-4, IL-5, IFN-gamma, IL-12, and TGF-beta in NP was significantly greater than in control NM tissues. The density of IL-4(+) and IL-5(+) cells in NP tissues significantly decreased after budesonide treatment from 40 +/- 12 to 17.8 +/- 8 and from 19.3 +/- 11 to 10.4 +/- 7, respectively. In contrast, the density of IFN-gamma(+) and IL-12(+) cells remained unchanged. In addition, we found that the density of TGF-beta(+) cells significantly increased after intranasal budesonide from 18 +/- 5 to 41 +/- 9. Third, damage to the entire length of the NP epithelium was quantified using a grading system. The epithelium of untreated NP was substantially damaged; remarkable epithelial restitution with no apparent changes in stromal collagen deposition was observed after intranasal budesonide treatment. CONCLUSIONS: These findings demonstrate that intranasal budesonide induced an increase in CD8 population and a selective regulatory effect on tissue cytokine expression. Furthermore, intranasal budesonide promoted epithelial remodeling. We hypothesize that these immunoregulatory and remodeling effects elicited by steroids might be, at least in part, mediated by the induction of TGF-beta. 相似文献
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Split tolerance between spleen and lymph node cells in severe combined immunodeficiency mice grafted with AKR fetal liver cells 总被引:1,自引:0,他引:1
Maeda Ken-ichi; Nagasawa Hideyuki; Furukawa Atsuko; Hisaeda Hajime; Himeno Kunisuke 《International immunology》1994,6(8):1213-1219
Severe combined Immunodeficient (SCID) mice defective in stemcells for T and B cells appear to be an ideal host for constructionof chimeric mice. When bone marrow cells are used as a sourceof stem cells, however, host SCID mice do not always show sufficientreconstitutlon. In this study, fetal liver cells from AKR embryoswere transplanted into SCID mice without prior irradiation.This treatment induced full reconstltution of lymphopoiesisas evaluated by flow cytometry analysis and serum Ig production2 months after transplantation. Thus, fetal liver cells seemto be a better source for reconstitutlon of SCID mice than bonemarrow cells. Lymph node (LN) cells of these mice (FLT mice)had no proliferatlve or cytotoxlc activities against eitherhost-type (C.B-17) or donor-type (AKR) spleen cells. However,spleen cells from FLT mice exhibited marked proliferatlve andcytotoxlc activities against C.B-17 cells, with no activitiesagainst AKR cells. Spirt tolerance against C.B-17 cells In spleenand LN cells was not a transient phenomenon, since similar resultswere obtained from a cytotoxic T lymphocyte assay 4 months later.In spite of the strong host reactivity in vitro, aberrationof clonal deletion or development of a graft-versus-host diseasewas not seen in FLT mice. As IL-2 induced the host reactivityof LN cells in a mixed lymphocyte reaction, potentially host-reactiveT cells were present in LN but were rendered anerglc. Tolerancein FLT mice seems to be regulated by a peripheral mechanism.We supposed that the split tolerance in FLT mice was inducedby the different antigenicity between the spleen and LN. 相似文献
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Atsuko Fujimoto Joseph W. Towner Allan J. Ebbin Emily J. Kahlstrom Miriam G. Wilson 《Journal of medical genetics》1974,11(3):287-291
A boy with unusual facial appearance and mental retardation was found to have duplication for the distal half of the long arm of chromosome No. 15 and possibly deficiency for the distal end of the long arm of No. 21. The chromosome abnormality was inherited from his mother, who had a translocation involving chromosomes Nos. 15 and 21. Giemsa-banding localized the break point in chromosome No. 15 just distal to the intense band at the midportion of the long arm. The break point in chromosome No. 21 appeared to be at the distal end of the long arm. The difficulty encountered in cytogenetic analysis of the propositus with conventional staining, the importance of chromosome analysis of the parents, and the application of differential staining techniques are also presented. 相似文献
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A Masunaga T Oka H Nakamura K Kinoshita T Yamashita I Sugawara S Itoyama 《Acta pathologica japonica》1992,42(12):916-922
A case of intrauterine tumor in a 62-year-old Japanese woman is presented. It was thought initially that this was a case of uterine tumor resembling an ovarian sex cord tumor. To examine the cytological features of the tumor cells, electron microscopical and immunohistochemical studies were done, and a hormone assay of the tumor tissue was performed. The tumor cells were rich in rough endoplasmic reticulum (rER), mitochondria and microfilaments. Some tumor cells tended to form glandular patterns, but these epithelial elements were frequently scattered among fibrous stromal elements. Though many tumor cells with an epithelial appearance possessed a large quantity of cytokeratin and vimentin, they did not secrete estradiol, progesterone, testosterone or human chorionic gonadotropin. This case was finally diagnosed as an intramural uterine stromal tumor with epithelial differentiation after taking all the available data into consideration. This would be classified as an endometrial stromal tumor with epithelial elements, recently proposed and named by Clement and Scully. 相似文献
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Immature dendritic cells (CD11c+ CD3- B220- cells) present in mouse peripheral blood 总被引:1,自引:0,他引:1
Adachi Y Toki J Ikebukuro K Tomita M Kaneda H Tanabe A Jun L Minamino K Suzuki Y Taketani S Ikehara S 《Immunobiology》2002,206(4):354-367
It is well known that dendritic cells (DCs) are developed from the peripheral blood of mice when peripheral blood mononuclear cells (PBMCs) are cultured with GM-CSF. We have previously found that immature DCs are present in the blood even in humans. In the present study, we show that CD11c+ CD3- B220- cells in the mouse peripheral blood are immature DCs. The percentage of CD11c+ CD3- B220- cells in the (PBMCs) of normal mice ranges from 0.5 to 2.5%. The CD11c+ CD3- B220- cells in the PBMCs show dendrites, similar in shape to the CD11c+ CD3- B220- cells in the spleen, which are thought to be DCs definitely. However, they have practically no capacity to stimulate the proliferation of allogeneic T cells, and show a lower expression of MHC class II, B7-1 and B7-2 than CD11c+ CD3- B220- cells in the spleen. When the CD11c+ CD3- B220- cells in the PBMCs are cultured with GM-CSF, they show not only the potent ability to stimulate the proliferation of allogeneic T cells but also a higher expression of MHC class II, B7-1 and B7-2. Moreover, they migrate into the spleen when they are injected intravenously. These results suggest that CD11c+ CD3- B220- cells in the PBMCs are immature DCs, and that they migrate into the spleen, where they mature. 相似文献