Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the mechanism of steroid resistance in lung fibrosis, cytokines expressed in the lung tissue of mice with bleomycin-induced lung fibrosis were studied. 1. Glucocorticoid administration (1 mg/kg/day) did not affect the grade of lung fibrosis induced by intratracheal injection of bleomycin (3.76 micrograms/g). 2. Cytokines expressed in the lung tissue were studied with the reverse-transcriptase polymerase chain reaction. Levels of promotor cytokines, such as TNF alpha, TGF beta, INF gamma, and IL-2, were significantly higher in lung tissue from the bleomycin group. The expression of these cytokines in the glucocorticoid group was low, especially the peak value. Expression of IL-4 was high in the bleomycin group, and was not inhibited in the glucocorticoid group. Expression of the down-regulator cytokine IL-10 was also high in the bleomycin group and very low in the glucocorticoid group. 3. The non-selectivity of glucocorticoids with respect to promotor and suppressive cytokines may account in part for steroid resistance in bleomycin-induced pulmonary fibrosis.
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PMID:[Steroid resistance and lung-tissue cytokines in experimental bleomycin-induced lung fibrosis]. 934 Dec 82

Interleukin (IL)-10 has been shown to reduce many inflammatory reactions. We investigated the in vivo effects of IL-10 on a bleomycin-induced lung injury model. Hemagglutinating virus of Japan (HVJ)-liposomes containing a human IL-10 expression vector (hIL10-HVJ) or a balanced salt solution as a control (Cont-HVJ) was intraperitoneally injected into mice on day -3. This was followed by intratracheal instillation of bleomycin (0.8 mg/kg) on day 0. Myeloperoxidase activity of bronchoalveolar lavage fluid and tumor necrosis factor-alpha mRNA expression in bronchoalveolar lavage fluid cells on day 7 and hydroxyproline content of the whole lung on day 21 were inhibited significantly by hIL10-HVJ treatment. However, Cont-HVJ treatment could not suppress any of these parameters. We also examined the in vitro effects of IL-10 on the human lung fibroblast cell line WI-38. IL-10 significantly reduced constitutive and transforming growth factor-beta-stimulated type I collagen mRNA expression. However, IL-10 did not affect the proliferation of WI-38 cells induced by platelet-derived growth factor. These data suggested that exogenous IL-10 may be useful in the treatment of pulmonary fibrosis.
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PMID:Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo. 1078 21

Various growth factors and cytokines have been suggested to play a central role in initiating and developing fibrosis in systemic sclerosis (SSc). To determine which serum levels of soluble mediators are the most relevant to the degree of skin sclerosis in SSc, serum levels of various soluble mediators were examined by ELISA and correlated with skin thickening that was measured using modified Rodnan total skin thickness scoring (TSS) system. Serum levels of IL-4, IL-12, IL-13, tumor necrosis factor-alpha, connective tissue growth factor (CTGF), vascular endothelial growth factor, monocyte chemotactic protein-1, macrophage inflammatory protein-1beta, soluble IL-6 receptor, and soluble L-selectin were higher in SSc patients than normal controls. Levels of IL-6, IL-10, and CTGF in patients with diffuse cutaneous SSc were higher than patients with limited cutaneous SSc and controls. Serum levels of IL-6 and IL-10 positively correlated with TSS in patients with SSc (r=0.625, P<0.0001 and r=0.663, P<0.0001, respectively). In addition, IL-10 levels significantly correlated with pulmonary fibrosis. Thus, serum levels of IL-6 and IL-10 most strongly reflect the extent of skin thickening in SSc, suggesting that levels of IL-6 and IL-10 are useful serological indicators for skin fibrosis in SSc.
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PMID:Serum levels of interleukin-6 and interleukin-10 correlate with total skin thickness score in patients with systemic sclerosis. 1153 78

Twenty-five subjects (24 males and 1 female, mean age 57.4 years) who have been exposed to asbestos underwent chest radiography, high resolution computed tomography (HRCT) of the chest, lung function tests and bronchoalveolar lavage (BAL) for evaluation of cell components (total cell count, percentages of macrophages, lymphocytes, neutrophil and eosinophil granulocytes and the lymphocyte subpopulations CD3+, CD4+, CD8+, CD19+ and HLADR+), soluble factors (IL-8, IL-10, IL-12 and MCP-1 in the supernatant) and concentration of asbestos fibre. The subjects were subdivided according to the degree of their exposure, to the concentration of asbestos fibres in the BAL and to chest X-ray findings using the I.L.O. classification (0/0pl, 0/1 and 1/0 and above). According to the exposure index, we showed statistically significant (p < 0.05) higher lymphocytes percentage in the BAL of subjects with moderate exposure and significantly higher levels of IL-10 (p < 0.05) in the supernatant of subjects showing an absence of asbestos fibres in their BAL. In the group of subjects with a 0/0 and 0/1 radiological profile, the cellular component of the BAL was characterised by a higher percentage of lymphocytes (p < 0.02), whereas a trend toward an increase in the number of neutrophils was noted in subjects with obvious pulmonary fibrosis. The percentage of neutrophils was inversely correlated with some parameters of respiratory function such as vital capacity (p = 0.03) and the partial pressure of oxygen (p = 0.05) in the blood. Investigating the cytokines in the supernatant of the BAL, we found a trend toward lower concentration of IL-10 in the group showing the worst radiological picture (I.L.O. > or = 1/0), and a statistically significant negative correlation between this cytokine and pO2 (p = 0.048). Concerning the other cytokines and chemokines studied (MCP-1, IL-8 and IL-12), no significant differences were found to be associated with the radiological profiles. There were, however, positive correlations between the concentration of IL-8 and the percentage of neutrophils (p = 0.038) and between the concentration of MCP-1 and the percentage of lymphocytes (p = 0.006). A negative relationship between the concentrations of IL-12 and IL-10 has been also observed (p = 0.028). This research allows us to hypothesise that IL-10 may have a pathogenetic role in the evolution of asbestosis.
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PMID:Immunocytological and mineralogical study of bronchoalveolar lavage in a group of subjects exposed to asbestos. 1287 99

Bleomycin yields pulmonary injury characterized by inflammation that proceeds to fibrosis. The production of IL-10 by pulmonary macrophages is increased in the inflammation that accompanies bleomycin lung injury. In the present study, IL-10 deficient and wildtype mice received 0.075 units of bleomycin intratracheally at day 0 and were sacrificed at day 7 or day 14. At day 7, pulmonary inflammation was increased in IL-10-deficient mice as reflected by increased representation of CD3+ and CD4+ lymphocytes and GR-1+ pulmonary granulocytes in the bronchoalveolar lavage (BAL) fluid. Pulmonary interstitial CD80+ and CD86+ mononuclear cells were increased in situ. At day 14, mononuclear cell inflammation was comparable between groups but pulmonary eosinophils were increased in the wildtype. There was no difference in the degree of pulmonary fibrosis, as judged by histology or lung hydroxyproline content. Lung chemokine expression of MIP-1alpha/beta, MIP-2, and eotaxin was increased at days 7 and 14 with a trend towards increased MCP-1 expression at day 14. The findings suggest an immunomodulatory role for IL-10 in the inflammatory response but not in the pulmonary fibrosis yielded by bleomycin.
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PMID:IL-10 inhibits inflammation but does not affect fibrosis in the pulmonary response to bleomycin. 1512 2

Systemic sclerosis (SSc) is a connective tissue disorder characterized by excessive collagen deposition in the skin and internal organs. Several cytokines and chemokines have been implicated in the induction of fibrosis, but a definitive relationship between specific cytokines and organ involvement has not been established yet. Serum samples, PBMC and T cell lines (TCL) obtained from 54 patients affected by SSc and 20 healthy donors (HD) were examined by ELISA for Interferon-gamma (IFN-gamma ), interleukin (IL)-4, IL-6, IL-10, IL-18, Transforming growth factor (TGF)-beta1, Tumour necrosis factor (TNF)-alpha, sCD30, Macrophage derived chemokine (MDC), Monocyte chemoattractant protein (MCP)-1, Macrophage inflammatory protein (MIP)-1alpha and Regulated on activation normal T-cell expressed and secreted (RANTES). In all the SSc serum samples, we found significantly increased levels of IL6, TNFalpha and MCP-1 but reduced amounts of gamma-IFN and MDC. IL6, IL10, IL18, MIP-1alpha and TNFalpha measured in supernatants from PHA-stimulated PBMC and IL6, MCP-1 and RANTES in supernatants from stimulated TCL were also increased in patients. MDC was decreased in all the biological SSc sources studied. TGF-beta1, IL10, and sCD30 were produced at a significantly lower level by SSc TCL. Serum IL6 and sCD30 levels were significantly increased in dc-SSc patients compared to lc-SSc as were levels of MCP-1 produced by PBMC and IL10 from TCL. We observed a strict relationship between pulmonary fibrosis and IL10, MCP-1 (both from TCL) and serum IL6. Kidney involvement was related to serum MCP-1 levels and IL18 production from PBMC. Oesophageal involvement correlated with MDC production from PBMC and IL10 synthesis by TCL. We showed that IL-6, IL-10, MDC and MCP-1 are variably associated with internal organ involvement and allow the discrimination between limited and diffuse forms of the disease.
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PMID:Cytokine and chemokine levels in systemic sclerosis: relationship with cutaneous and internal organ involvement. 1554 34

The role of interleukin (IL)-18 in the protection from interstitial pneumonia and pulmonary fibrosis induced by bleomycin (BLM) was investigated by comparing the severity of BLM-induced lung injuries between wild-type and C57BL/6 mice with a targeted knockout mutation of the IL-18 gene (IL-18-/- mice). IL-18-/- mice showed much worse lung injuries than wild-type mice, as assessed by the survival rate, histological images, and leukocyte infiltration in the bronchoalveolar lavage fluid and myeloperoxidase activity. In wild-type mice, administration of IL-18 before BLM instillation resulted in suppression of lung injuries, increases in the hydroxyproline content, and decreases in the granulocyte-macrophage colony-stimulating factor content in the lung. Preadministration of IL-18 also resulted in prevention of the reduction of the lung IL-10 content caused by BLM-induced damage of alveolar epithelial. BLM instillation suppressed superoxide dismutase (SOD) activity in IL-18-/- mice to a greater extent than in wild-type mice. Pretreatment of IL-18 augmented Mn-containing superoxide dismutase (Mn-SOD) messenger RNA expression and SOD activity in the lung and prevented the reduction of SOD activity caused by BLM in both wild-type and IL-18-/- mice. These results suggest that IL-18 plays a protective role against BLM-induced lung injuries by upregulating a defensive molecule, Mn-SOD.
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PMID:Protection against bleomycin-induced lung injury by IL-18 in mice. 1579 64

GILZ (glucocorticoid-induced leucine zipper), a gene induced by dexamethasone, is involved in control of T lymphocyte activation and apoptosis. In the present study, using Gilz transgenic mice (TG), which overexpress GILZ in the T-cell lineage, we demonstrate that Gilz is implicated in T helper-2 (Th-2) response development. After in vitro stimulation by CD3/CD28 antibodies, peripheral naive CD4+ T cells from TG mice secrete more Th-2 cytokines such as interleukin-4 (IL-4), IL-5, IL-13, and IL-10, and produce less Th-1 cytokines such as interferon-gamma (IFN-gamma) than wild-type mice (WT). CD4+ TG lymphocytes up-regulated Th-2 cytokine expression in the specific response to ovalbumin chicken egg (OVA) antigen immunization. Up-regulation correlated with increased expression of GATA-3 and signal transducer and activator of transcription 6 (Stat6), Th-2-specific transcription factors and decreased expression of T-bet, a transcription factor involved in Th-1 differentiation. Finally, in TG mice delayed-type hypersensitivity, a Th-1 response, was inhibited and bleomycin-induced pulmonary fibrosis, a Th-2 mediated disease, was more severe. These results indicate that Gilz contributes to CD4+ commitment toward a Th-2 phenotype and suggest this contribution may be another mechanism accounting for glucocorticoid immunomodulation.
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PMID:Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines. 1620 13

The immunoregulatory cytokine IL-10 plays an essential role in down-modulating adaptive and innate immune responses leading to chronic inflammatory diseases. In contrast, cysteinyl leukotrienes (cysLTs), important proinflammatory mediators of cell trafficking and innate immune responses, are thought to enhance immune reactions in the pathogenesis of diseases, such as bronchial asthma, atherosclerosis, and pulmonary fibrosis. The aim of this study was to determine the IL-10 regulatory role in cysLT-induced activation of human monocytes and monocyte-derived dendritic cells. Herein we show that cysLT-induced activation and chemotaxis of human monocytes and monocyte-derived immature dendritic cells (iDC) are inhibited by IL-10 pretreatment. IL-10 down-regulated cysLT type 1 and 2 receptors' mRNA in a time- and concentration-dependent fashion. cysLT-induced activation of monocytes and iDCs measured by intracellular calcium flux and immediate-early gene expression (FBJ murine osteosarcoma viral oncogen homolog B and early growth response-2) was potently decreased by IL-10 and by the cysLT antagonist MK571. Chemotaxis of monocytes and iDCs to increasing concentrations of leukotriene D(4) (LTD(4)) was also inhibited by IL-10. LTD(4) enhanced iDC migration in response to CCL5. IL-10 selectively inhibited LTD(4)-induced chemotaxis without affecting migration to CCL5. These data indicate that cysLT-induced activation of human monocytes and dendritic cells may be specifically inhibited by IL-10, suggesting a direct link between the 5-lipoxygenase proinflammatory pathway and IL-10 regulatory mechanisms. Antileukotriene therapies may reproduce some regulatory mechanisms played by IL-10 in inflammatory processes.
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PMID:IL-10 inhibits cysteinyl leukotriene-induced activation of human monocytes and monocyte-derived dendritic cells. 1849 Jul 62

In order to evaluate the degree of pulmonary fibrosis and to identify the fibrogenic mechanisms induced by ultrafine amorphous silica (UFAS), UFAS suspensions ( approximately 50microl) were instilled intratracheally into A/J mice at doses of 0, 2, 10 and 50mg/kg (n=5 per group). Mice were sacrificed at 24h, 1, 4 and 14 weeks after exposure. Gomori's trichrome staining revealed that UFAS induced severe alveolar epithelial thickening and pulmonary fibrosis at 1 week, though animals almost recovered at 4 and 14 weeks. The mRNA and protein levels of cytokines (IL-4, IL-10, IL-13 and IFN-gamma), matrix metalloproteinases (MMP-2, MMP-9 and MMP-10) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in lung tissues were significantly elevated at 24h and 1week post-treatment, though these levels decreased to near the control range at 4 and 14 weeks except IFN-gamma and MMP-2. These results demonstrate that UFAS can induce pulmonary fibrosis in the same way as crystalline silica. However, the degree of fibrosis observed was transient. This study shows that cytokines (IL-4, IL-10, IL-13 and IFN-gamma), MMPs (MMP-2, MMP-9 and MMP-10) and TIMP-1 play important roles in the fibrosis induced by the intratracheal instillation of UFAS.
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PMID:Transient pulmonary fibrogenic effect induced by intratracheal instillation of ultrafine amorphous silica in A/J mice. 1883 41


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