Objective. The mechanisms by which monocyte/ macrophage cells migrate to the joint involve a series of integrated adhesion and signaling events in which chemokines and their receptors are strongly implicated. This study was undertaken to investigate the hypothesis that stromal cell-derived factor 1 (SDF-1), a CXC chemokine (CXCL12), plays a critical role in monocyte/ macrophage localization to synovium.Methods. SDF-1 and CXC receptor 4 (CXCR4) expression in rheumatoid arthritis (RA) and osteoarthritis synovium and graft SDF-1, tumor necrosis factor ␣ (TNF␣), and human and murine vascular markers were examined by immunohistochemistry and doubleimmunofluorescence. The functional capacity of SDF-1 to modulate monocyte migration into joints was investigated by examining the localization of promyelomonocytic U937 cells into synovial tissue transplanted into SCID mice. SDF-1, TNF␣, or saline was injected into graft sites and response determined by the number of fluorescently labeled U937 cells (injected intravenously) detected in grafts by ultraviolet microscopy.Results. SDF-1 and CXCR4 were highly expressed in CD68؉ cells in the RA synovium. SDF-1 induced U937 cell migration in vitro and in vivo in a dosedependent manner and, in vivo, SDF-1 was more effective than TNF␣. In contrast to TNF␣, SDF-1 did not induce intracellular adhesion molecule 1 in transplant microvasculature. Furthermore, intragraft injection of SDF-1 did not up-regulate TNF␣, or vice versa.Conclusion. This study demonstrates, for the first time, that SDF-1 is functional in vivo when injected into synovial grafts. In addition, SDF-1 is more potent than TNF␣, and its mechanisms of action appear to be autonomous. Therefore, SDF-1 may be an important TNF-independent molecule involved in the migration to and retention of inflammatory effector cells in the joint.
SUMMARYAdhesion mechanisms play a major role in the recruitment of peripheral blood lymphocytes (PBL) which characteristically infiltrate rheumatoid arthritis (RA) synovium and other chronically inflamed tissues. Through a sequential series of complex integrated adhesion and signalling events,`multistep model of migration', specific subsets of PBL are recruited into inflamed tissues. In this process both leucocyte receptors and microvascular endothelial (MVE) counter-receptors play a critical role. The MVE in particular, during an inflammatory state, is the target of various inflammatory mediators that cause the up-regulation of several cell adhesion molecules (CAM). One of the most important factors known to be a powerful inducer of MVE CAM is TNF-a . Conversely, blocking TNF-a causes a downmodulation of CAM expression. To test directly the capacity of TNF-a to induce cell migration into RA synovium we adapted a model in which synovial grafts were implanted into SCID mice subcutaneously.Using this model we demonstrate that: (i) transplants remain viable and become vascularized and fed by mouse subdermal vessels; (ii) the mouse vasculature connects to the transplant vasculature which maintains the ability to express human CAM; (iii) intragraft injections of TNF-a up-regulate the expression of human CAM, following the down-regulation which occurred 4 weeks post-transplantation; and (iv) the up-regulation of graft CAM is associated with increased human PBL migration into the transplants. This study provides direct evidence in vivo of the capacity of TNF-a to induce cell migration. In addition, it provides the experimental background for the optimal use of this model.
BackgroundAsthma is a chronic inflammatory disorder of airway that involves many cells and elements. Chronic inflammation caused by increase Airway hyperresponsiveness that cause recurrent episodic symptoms of breathlessness, wheezing, chest tightness and coughing, especially at night or early morning. Interleukin 17F is a cytokine that plays an important role in the pathophysiology of asthma attacks. Some studies show a variety of IL-17F roles in the pathogenesis of airway inflammation due to an allergic reaction.ResultsThe study was conducted at the Prof. Dr. R. D. Kandou Manado Hospital, Indonesia. Samples were taken continuously until the number of meant samples was achieved. Blood samples were collected from 40 atopic asthmatic patients. From statistical analysis based on the hypothesis, there was positive correlation between mRNA levels of IL-17F and IL-17F in atopic asthmatic patient (p = 0.000 and r = 0.988).ConclusionsAccording these data suggest that levels of mRNA IL-17F and IL17F might be useful parameters for the diagnosis of atopic asthma patient.
Background Around 70% of breast cancers (BCs) are estrogen receptor-α (ERα)-positive. Adjuvant endocrine therapy is used to reduce estrogen levels and inhibit signal transduction through the ER. The anti-estrogen drugs that are most commonly used in endocrine therapy belong to the selective ER modulator (SERM) class and include tamoxifen. Although it has been used for three decades in cases of early-stage and ERα-positive BC, resistance to tamoxifen is a common problem. microRNAs (miRNAs) have a potential role in demonstrating BC resistance to tamoxifen therapy. Hence, there is a need to investigate the expression of miRNA-221 (miR-221) in luminal-subtype BC patients receiving tamoxifen therapy. Methods This case-control study investigated luminal-subtype BC patients who had undergone endocrine therapy for at least 1 year. The case group comprised patients with local or metastatic recurrence, and the control group comprised patients without local or metastatic recurrence. Results There was a significant difference in miR-221 expression ( p = 0.005) between the case and control groups. There were no significant differences between the groups that were positive and negative for the progesterone receptor (PR) ( p = 0.25), had high and low marker of proliferation Ki-67 levels ( p = 0.60), were positive and negative for lymphovascular invasion ( p = 0.14), and had stage 2 and stage 3 cancer ( p = 0.25). Conclusion miR-221 expression was higher in tamoxifen-resistant BC cases. miR-221 is a potential biomarker of tamoxifen resistance.
Primary cultures of liver cells isolated from adult rats by trypsin and collagenase perfusion techniques were carried out to compare cytologic and biochemical properties between the differently prepared cells. Trypsin-dispersed cells consisted of comparatively smaller cells, whereas collagenase-dispersed cells consisted of larger cells. The cell attachment efficiency on culture day 1 was about twice as high in the liver cells prepared with collagenase than those prepared with trypsin. Mature hepatocytes isolated by collagenase perfusion could be maintained in the primary culture for a longer period than those isolated by trypsin perfusion. Epithelial-like clear cells started to grow much earlier in the primary culture of the trypsin-dispersed liver cells than in that of the collagenase-dispersed liver cells. Earlier proliferation of epithelial-like clear cells could not be induced by in vitro trypsinization of the collagenase-dispersed liver cells. Both kinds of enzymatically prepared liver cells showed albumin production and exhibited glucose 6-phosphatase (D-glucose-6-phosphate phosphohydrolase, EC 3.1.3.9, G6Pase) and tyrosine aminotransferase (L-tyrosine: 2-oxoglutarate amino-transferase, EC 2.6.1.5, TAT) activities for 1 week in the primary culture. Albumin production was higher in the liver cells prepared with collagenase than those prepared with trypsin, whereas G6Pase activity was almost the same between them. TAT activity up to culture day 2 was about 3-fold higher in the liver cells prepared with collagenase than in those prepared with trypsin. Combined supplementation of dexamethasone (1 X 10(-5)M) and insulin (10 micrograms/ml) consistently improved the cell attachment efficiency and was very effective in the maintenance of mature hepatocytes in both types. Furthermore, these hormones enhanced the albumin production and TAT activity in both types.
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