A Case of Pulmonary Hemorrhage Associated with IgA Nephropahty in Adult / 대한신장학회잡지

IgA nephropathy is the most common glomerulonephritis in all parts of the world. It presents as asymptomatic microscopic hematuria or proteinuria or as episodic gross hematuria after upper respiratory infection or excercise. Pulmonary hemorrhage is both a rare complication and presentation of IgA nephropathy. We report a case of pulmonary hemorrhage associated with IgA nephropathy in adult. A 29-year-old woman was transferred because of gross hematuria and hemoptysis after hysterectomy. Chest X-ray showed bilateral pulmonary infiltrates in lower lobes. Renal biopsy showed mesangial expansion by mesangial cellular proliferation with mesangial staining of IgA. Her repiratory symptom and pathcy opacities on the chest X-ray disappeared spontaneously. Normal renal function of the patient maintained but she had persistent hematuria.

The Production and Correlation of Silica Induced Proinflammatory Cytokines and TGF-beta from Monocytes of Balb/C Mice / 결핵

BACKGROUND: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica they liberate the pro-inflammatory cytokines such as IL-i/A IL-C, TNF-a and fibrogenic cytokines, TGF-beta and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGP-beta, a fibrogenic cytokine, have not been defined, yet In this study, we investigated silica induced IL-1/beta, IL-6, TNF-alpha and TGF-beta production and the effect of IL-1/beta, IL-6, TNF-alpha on the production of TGF-beta from lung macrophages of Balb/C mice. METHOD: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica (SiO2) in the various concentration for 2, 4, 8, 12, and 24 bows. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. RESULTS: The production of IL-6 was not observed till 4 hours, and reached the peak levels at S horns after stimulation of silica. The production of TNF-alpha increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-beta production reached the peak levels at 24 hours. TNF-alpha upregulated the silica induced TGF-beta production Silica induced TGF-beta production was hooked by pretreated anti-TNF-alpha antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours in TNF-alpha and 12 hours in TGP-beta. CONCLUISON: The results above suggest that silica induced the sequential production of IL-6, TNF-alpha and TGF-beta from macrophages and TNF-alpha upregultaes the production of TGF-beta from silica-induced macrophages.

Silica induced Expression of IL-1beta, IL-6, TNF-beta, TGF-alpha, in the Experimental Murine Lung Fibrosis / 결핵

BACKGROUND: Silica-induced lung diseases is characterized by the accumulation of inflammatory cells at early stage and fibrosis in pulmonary parenchyma and interstitium at late stage. As a consequence of inflammation, silicosis is accompanied with the expansion of interstitial collagen and the formation of fibrotic nodule. In this process, several kinds of lung cells produce cytokines which can amplify and modulate pulmonary fibrosis. The alveolar macrophage is a potent source of proflammatory cytokines and growth factor. But in the process of silicotic inflammation and fibrosis, there are many changes of the kinetics in cytokine network. And the sources of cytokines in each phase are not well mown. METHOD: 2.5 mg of silica was instillated into the lung of C57BL/6J mice. After intratracheal instillation of silica, the lungs were removed for imunohistsochemical stain at 1. 2,7 day, 2, 4,8, 12 week, respecilvely. We investigated the expression of IL-1beta, IL-6, TNF-alpha and TGF-beta in lung tissue. RESULTS: 1) The expression of IL-6 increased from 1 day after exposure to S weeks in vascular endothelium. Also peribronchial area were stained for IL-6 from 7 days and reached the peak level for 4 weeks. 2) The IL-1beta was expressed weakly at the alveolar and peribronchial area through 12 weeks. 3) The TNF- expressed strongly at alveolar and bronchial epithelia during early stage and maintained for 12 weeks. 4) TGF-beta was expressed strongly at bronchial epithelia and peribronchial area after 1 week and the strongest at 8 weeks. CONCLUISON: The results above suggests IL-6, TNF- appear to be a early inflammatory response in silica induced lung fibrosis and TGF-beta play a major role in the maintenance and modulation of fibrosis in lung tissue. And the regulation of TNF- production will be a key role in modultion of silica-induced fibrosis.

Lipopolysaccharide-induced Synthesis of IL-1beta, IL-6, TNF-alpha and TGF-beta by Peripheral Blood Mononuclear Cells / 결핵

BACKGROUND: Endotoxin (LPS lipopolysaccharide), a potent activator of immune system, can induce acute and chronic inflammation through the production of cytokincs by a variety of cells, such as monocytes, endothelial cells, lymphocytes, eosinophils, neutrophils and fibroblasts. LPS stimulate the mononucelar cells by two different pathway, the CD14 dependent and independent way, of which the former has been well documented, but not the latter. LPS binds to the LPS-binding protein (LBP), in serum, to make the LPS-LBP complex which interacts with 0D14 molecules on the mononuclear cell surface in peripheral blood or is transported to the Ussues. In case of high concentration of LPS, LPS can stimulate directly the macrophages without LBP. We investigated to detect, the generation of proinflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-alpha, and fibrogenic cytokine, TGF-beta, by peripheral blood mononuclear cells (PBMC) after LB'S stimulation under serum-free conditions, which lacks LBPs. METHODS: PBMC were obtained by centrifugation on Ficoll Hypaque solution of peripheral venous bloods from healthy normal subjects, then stimulated in the presence of LPS (0.1 microgram/mL to 100 microgram/mL). The activities of IL-1, IL-6, TNF, and TGF-betawere measured by bioassaies using cytokines - dependent proliferating or inhibiting cell lines. The cellular sources producing the cytokines was investigated by immunohistochemical stains and in situ hybridization. RESULTS: PBMC started to produce IL-6, TNF-alpha and TGF-beta in 1 hr, 4 hrs and 8hrs, respectively, after LPS stimulation The production of IL-6, TNF-alpha and TGF-beta continuously increased 96 His after stimulation of LPS. The amount of production was 19.8 ng/ml of IL-6 by 105 PEMC, 4.1 ng/mL of TNF by 106 PBMC and 344 pg/mL of TGF-betaby 2 x 106 PBMC. The immunoreactivity to IL-6, TNF-alpha and TGF-betawere detected on monocytes in LPS-stimulated PBMC. Some of lymphocytes showed positive immunoreactivity to TGF-beta. Double immunohistochemical stain showed that IL-1beta, IL-6, TNF-alpha expression was not associated with CD14 postivity on monocytes. IL-1beta, IL-6, TNF-alpha and TGF-/betamRNA expression worn same as observed in immunoreactivity for each cytokines. CONCLUISON: When monocytes are stimulted with LPS under serum-free conditions, IL-6 and TNF-alphaare secreted in early stage of inflammation. In contrast, the secretion of TGF-beta arise in the late stages and that N maintained after 96 his. The main cells releasing lL-1beta, IL-6, INF-alpha and TGF-beta are monocytes, but also lymphocytes can secret TGF-beta.

The Effects of Proinflammatory Cytokines and TGF-beta, on The Fibroblast Proliferation / 결핵

BACKGROUNDS: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (lL-1) and/or tumor necrosis factor (TNF). It has ken well known that TGF-beta enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collgen. In this regard, It is likely that TGF-beta undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-beta, IL-1, IL-6 and TNF-alpha regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of 'PGF-beta, IL-1beta, IL-6 and TNF-alpha and their effect on the proliferation of fibroblasts. METHODS: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. RESULT: In the medium containg 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1beta, TNF-alpha and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1beta and TNF-a enhanced TGF-beta-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-beta-induced proliferation. And TNF-alpha-induced proliferation of MRC-5 was reduced by IL-1beta in 50%. TGF-beta, TNF-alpha and both induced the proliferation of MRC-5 to 89%, 135% and 222 %, respectively. CONCLUSIONS: TNF-alpha TGF-beta and lL-1beta, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-alpha and IL-1beta enhance the TGF-beta-induced proliferation of MRC-5, but IL-6 did not have any effect. TNF-alpha-induced proliferation of MRC-5 is diminished by IL-i, and TNF-alpha and TGF-beta showed a additive effect.