Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IL-12p40 is known as a component of the bioactive cytokines interleukin (IL)-12 and IL-23 but it is not widely recognized as having intrinsic functional activity. Recent publications have altered this perception and support an independent role for IL-12p40. IL-12p40 is induced in excess over the other subunits of IL-12 and IL-23 and can exist in a monomeric or homodimeric form. Its most widely appreciated function is to provide a negative feedback loop by competitively binding to the IL-12 receptor. However, IL-12p40 acts as a chemoattractant for macrophages and promotes the migration of bacterially stimulated dendritic cells. It is associated with several pathogenic inflammatory responses such as silicosis, graft rejection and asthma but it is also protective in a mycobacterial model. An appreciation of the independent function of IL-12p40 is important for improving our understanding of both protective and pathogenic immune responses.
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PMID:IL-12p40: an inherently agonistic cytokine. 1712 1

IL-17-producing T lymphocytes play a crucial role in inflammation, but their possible implication in fibrosis remains to be explored. In this study, we examined the involvement of these cells in a mouse model of lung inflammation and fibrosis induced by silica particles. Upregulation of IL-17A was associated with the development of experimental silicosis, but this response was markedly reduced in athymic, gammadelta T cell-deficient or CD4(+) T cell-depleted mice. In addition, gammadelta T lymphocytes and CD4(+) T cells, but not macrophages, neutrophils, NK cells or CD8 T cells, purified from the lungs of silicotic mice markedly expressed IL-17A. Depletion of alveolar macrophages or neutralization of IL-23 reduced upregulation of IL-17A in the lung of silicotic mice. IL-17R-deficient animals (IL-17R(-/-)) or IL-17A Ab neutralization, but not IL-22(-/-) mice, developed reduced neutrophil influx and injury during the early lung response to silica. However, chronic inflammation, fibrosis, and TGF-beta expression induced by silica were not attenuated in the absence of IL-17R or -22 or after IL-17A Ab blockade. In conclusion, a rapid lung recruitment of IL-17A-producing T cells, mediated by macrophage-derived IL-23, is associated with experimental silicosis in mice. Although the acute alveolitis induced by silica is IL-17A dependent, this cytokine appears dispensable for the development of the late inflammatory and fibrotic lung responses to silica.
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PMID:IL-17A-producing gammadelta T and Th17 lymphocytes mediate lung inflammation but not fibrosis in experimental silicosis. 2042 47

The aim of the present study was to investigate the correlation between tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12p40-containing cytokines, in silicosis patients and healthy donors exposed to silica dust, in an attempt to clarify the reason for variety of clinical outcomes between humans with similar exposure history. Serum levels of TNF-alpha, IL-12p40, IL-12p70 and IL-23 in total group of 62 silicosis patients, 24 healthy donors with similar exposure history like patients and 19 healthy donors without exposure were determined by enzyme-linked-immunosorbent assay (ELISA) method. The serum level of TNF-alpha was significantly higher in healthy donors exposed to SiO(2) (22.4 +/- 11.1 pg/mL) in comparison with non-exposed healthy donors (14.8 +/- 8.8 pg/mL; p = 0.022) and similar to that in silicosis patients. In total, group of silicosis patients significantly elevated levels of TNF-alpha (20.9 +/- 12.9 vs. 14.8 +/- 8.8 pg/mL; p = 0.047) and IL-12p40 (94.5 +/- 51.6 pg/mL vs. 68.7 +/- 26.2 pg/mL; p = 0.029) compared to non-exposed healthy donors were observed. In addition, a strong positive correlation between TNF-alpha and IL-23 levels (r = 0.678; p = 0.022) and between TNF-alpha and IL-12p70 levels (r = 0.75; p = 0.0003) was detected in the group of exposed healthy donors, while in the group of silicosis patients, a significant positive correlation was observed only between TNF-alpha and IL-12p40 (r = 0.434; p = 0.00048), in contrast to other IL-12p40 containing cytokines. In conclusion, we could assume that the elevated serum levels of TNF-alpha are associated with exposition to silica particles, while the elevation of both TNF-alpha and IL-12p40 is associated with silicosis development and severity. Additionally, the balance between IL-12p40-containing cytokines may also contribute to the silicosis progression.
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PMID:Correlation between TNF-alpha and IL-12p40-containing cytokines in silicosis. 2052 62

Silicosis is an inflammatory and fibrotic lung disease caused by inhalation of silica. Th17 cells play a key role in causing silica-induced lung inflammation and fibrosis. Baicalin, a compound isolated from the Chinese herb Huangqin, could suppress the differentiation of Th17 cells and alleviate inflammation. However, there are very few reports of the immunoregulatory mechanisms of baicalin in experimental silica-induced lung inflammation and fibrosis. In our study, mice were exposed to silica by intratracheal instillation, and in this way we established an experimental silicosis model. To elucidate the effects and mechanisms of baicalin in silica-induced inflammation and fibrosis, we used baicalin to treat the developed mouse model of silicosis. Treatment with baicalin attenuated the accumulation of inflammatory cells and led to milder pathological inflammatory and fibrotic changes in lung tissues. Baicalin affected the immunological balance between Th17 and Treg responses. Therefore, baicalin caused a decrease in Th17 cells by stimulating Treg cells and by inhibiting IL-6 and IL-23. We further demonstrated that silica-induced Th1 and Th2 immune responses were both inhibited by increased Treg activation, which was promoted by baicalin. Our findings confirmed the potential functions of baicalin in inhibiting the Th17 response and reducing silica-induced inflammation and fibrosis.
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PMID:Baicalin Alleviates Silica-Induced Lung Inflammation and Fibrosis by Inhibiting the Th17 Response in C57BL/6 Mice. 2660 88