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

Silicosis is primarily a mononuclear cell inflammatory and fibrotic disease of the pulmonary parenchyma. It is known that lung-associated lymph nodes are also affected. To study the involvement of lymphocytes in silicosis, we examined lymph nodes of rats 12 months after an 8-day silica aerosol exposure. We found that 2 thoracic lymph nodes close to the thymus were enormously enlarged in silicotic rats and contained a 49-fold higher cell number than control lymph nodes. The higher cell number was caused by parallel increases in T- and B-lymphocytes, natural killer (NK) cells, and macrophages without change in the relative proportions when compared with control thoracic lymph nodes. By examining interleukin-2 (IL-2) receptor and intercellular adhesion molecule-1 expression, we detected a significantly higher percentage of activated CD8+ T cells and, to a lower degree, of CD4+ T cells in thoracic lymph nodes of silicotic animals. In contrast, no differences in the activation state were found in T cells obtained from cervical or mesenteric lymph nodes of silicotic and control rats. The occurrence of activated T cells in thoracic lymph nodes of silicotic rats was documented further by selectively enhanced interferon-gamma (IFN-gamma) mRNA expression in the absence of IL-2 and IL-4 mRNA changes. These data show that T-lymphocytes of thoracic lymph nodes have become activated with an enhanced IFN-gamma gene transcription which may be an important cause of macrophage activation during silicosis.
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PMID:T-lymphocyte activation in the enlarged thoracic lymph nodes of rats with silicosis. 907 Jun 16

Tetrandrine, a purified traditional Chinese medicinal herb that acts as an immunosuppressant and a Ca2+ channel blocker, has been clinically used to treat patients with arthritis, silicosis and hypertension. Since T cells play a critical role as autoreactive and pathogenic population in autoimmune diseases, in this study, we examined the immunosuppressive effect of tetrandrine on human peripheral blood T cells. We showed that tetrandrine inhibited phorbol 12-myristate 13-acetate (PMA) + ionomycin-induced T cell proliferation, interleukin-2 secretion and the expression of the T cell activation antigen, CD71. Further investigation of the molecular mechanism demonstrated that tetrandrine inhibited the expression of the protein kinase C-dependent interleukin-2 receptor alpha chain and CD69 but not the expression of the Ca2+-dependent CD40 ligand and CD69. Interestingly, when tetrandrine and cyclosporin A were added together, significant synergism in the suppression of T cell activation was observed. Moreover, of the several tetrandrine analogues studied, hernandezine was the most potent inhibitor of protein kinase C signaling events. These results also suggest that the protein kinase C-inhibitory capacity of tetrandrine and its analogues may not be associated with their function as Ca2+ channel blockers. Lastly, we showed that, within therapeutic concentrations, tetrandrine and its analogues could induce cellular apoptosis, which is defective in autoimmune diseases. In conclusion, our findings provide novel information about the molecular mechanism of the immunosuppressive effect of tetrandrine and its analogues in human peripheral blood T cells.
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PMID:Plant alkaloid tetrandrine downregulates protein kinase C-dependent signaling pathway in T cells. 1007 15