Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UMLS:C0409974 (
lupus
)
22,386
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Next to oxygen silicium is the most common substance of our environment. It occurs mostly in form of quartz (
SiO2
). In the past silica was usually mentioned in connection with foreign body granulomas in dermatological papers. Recently relations between occupational silica exposure and several diseases were reported. Silica exposure was related to the development of scleroderma,
lupus
erythematodes and sarcoidosis. Pathogenetic connections may be due to a stimulating effect on fibroblasts and due to immunmodulating properties of silica.
...
PMID:[Quartz--its relevance for dermatology]. 283 Oct 19
Crystalline silica
(cSiO
2
) is a widely recognized environmental trigger of autoimmune disease. In the
lupus
-prone female NZBWF1 mouse, airway exposure to cSiO
2
triggers pulmonary ectopic lymphoid neogenesis, systemic autoantibody elevation, and glomerulonephritis. Here we tested the hypothesis that upregulation of adaptive immune function genes in the lung precedes cSiO
2
-triggering of autoimmune disease in this model. The study include three groups of mice, as follows: (1) necropsied 1 d after a single intranasal instillation of 1 mg cSiO
2
or vehicle, (2) necropsied 1 d after four weekly single instillations of 1 mg cSiO
2
or vehicle, or (3) necropsied 1, 5, 9, or 13 weeks after four weekly single instillations of 1 mg cSiO
2
or vehicle. NanoString nCounter analysis revealed modest transcriptional changes associated with innate and adaptive immune response as early as 1 d after a single cSiO
2
instillation. These responses were greatly expanded after four weekly cSiO
2
instillations. Concurrent with ectopic lymphoid neogenesis, dramatic increases in mRNAs associated with chemokine release, cytokine production, sustained interferon activity, complement activation, and adhesion molecules were observed. As disease progressed, expression of these genes persisted and was further amplified. Consistent with autoimmune pathogenesis, the time between 5 and 9 weeks post-instillation reflected an important transition period where considerable immune gene upregulation in the lung was observed. Upon termination of the chronic study (13 weeks), cSiO
2
-induced changes in transcriptome signatures were similarly robust in kidney as compared to the lung, but more modest in spleen. Transcriptomic signatures in lung and kidney were indicative of infiltration and/or expansion of neutrophils, macrophages, dendritic cells, B cells, and T cells that corresponded with accelerated autoimmune pathogenesis. Taken together, airway exposure to cSiO
2
elicited aberrant mRNA signatures for both innate and adaptive immunity that were consistent with establishment of the lung as the central autoimmune nexus for launching systemic autoimmunity and ultimately, kidney injury.
...
PMID:Mapping of Dynamic Transcriptome Changes Associated With Silica-Triggered Autoimmune Pathogenesis in the Lupus-Prone NZBWF1 Mouse. 3098 95
