Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease (IBD) that almost always affects the rectal mucosa and variable length of the colon in continuity and at times mucosa of the entire colon. It is not caused by any specific pathogen. Genetics, environmental factors and altered immune responses to dietary macromolecules, colonic bacteria and cellular proteins have been implicated in the pathogenesis of UC. Autoimmune response against cytoskeletal, microfilament protein tropomyosin (Tm) seems to play an important role in the pathogenesis of UC. The predominant colonic epithelial Tm isoform, hTm5, can induce both humoral (B-cells) and cellular (T-cells) response in patients with UC. Such responses are not seen in normal subjects and disease control subjects, such as patients with Crohn's disease (CD, another type of IBD) and patients with lupus. A novel observation that hTm5 is expressed on colon epithelial cell surface but not on small intestinal epithelial cells provides evidence for presentation to immune effector cells. This surface expression of hTm5 seems to be facilitated by a colon epithelial cell membrane associated protein, CEP, that acts as a chaperone for the trans-migration of hTm5 to the surface and both hTm5 and CEP are then released outside the cell. Both CEP and hTm5 expression are increased with pro-inflammatory cytokine, such as gamma-interferon. hTm5 expression in UC mucosa is also significantly increased compared to normal. Finally, autoantibodies against hTm5 observed both in circulation and in the colon mucosa of patients with UC are pathogenic causing colon epithelial cell destruction by antibody and complement mediated cytolysis.
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PMID:Tropomyosins in human diseases: ulcerative colitis. 1920 21

Current therapies for late-stage systemic lupus erythematosus (SLE) are limited to cytotoxic agents. Delanzomib (CEP-18770) is an orally active, reversible P2 threonine boronic acid inhibitor of the 26S mammalian proteasome. Delanzomib was tested in a head-to-head comparison against bortezomib to protect and treat mice with fatal lupus nephritis (LN). Age matched MRL/lpr or NZBWF1 mice with established SLE or LN, respectively, were treated with delanzomib either 3 mg/kg once or twice weekly intravenously or orally at 10 mg/kg. Mice were also treated with reference agent bortezomib at 0.5 mg/kg, intraperitoneally, once a week or 0.3 mg/kg once or twice a week. Reductions in the frequencies of specific anti-chromatin, smith and dsDNA antibody secreting cells and levels of the corresponding circulating antinuclear antibodies, were observed following delanzomib treatment. Reductions in several serum pro-inflammatory cytokines were observed in delanzomib-treated animals. Delanzomib treatment suppressed the development and progression of renal tissue damage and extended the survival of ill mice. Proteinuria was significantly decreased and severity of various renal histopathologies reduced relative to vehicle-treated nephritic mice. Treatment of lupus in these models demonstrated that delanzomib treatment lead to greater tolerability and rate of response resulting in improved stabilization of disease.
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PMID:Novel, orally active, proteasome inhibitor, delanzomib (CEP-18770), ameliorates disease symptoms and glomerulonephritis in two preclinical mouse models of SLE. 2217 95

Systemic lupus erythematosus is a systemic autoimmune disease characterized by the presence of myriad autoantibodies, some with pathogenic potential, and diverse clinical manifestations. Involvement of the kidney is a major cause of morbidity and mortality in human lupus patients and in murine models of the disease. It is hoped that more specific inhibition of crucial disease pathways would improve patient response rates, while reducing the considerable rates of drug-related side effects associated with current therapy. IL-6 has a pivotal regulatory role in the development and maturation of long-lived plasma cells, one of the key cell types driving the lupus disease phenotype as the source for the majority of lupus-related autoreactive antibodies. In this study, Lu et al. target the IL-6 signal transduction pathway using a specific JAK2 inhibitor of the JAK-STAT pathway, CEP-33779. In murine lupus models, they show significant improvement in nephritis, and prolonged survival, in mice treated with CEP-33779. The study presents the promise of a novel pathway for therapeutic intervention in systemic lupus erythematosus using a medication administered orally.
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PMID:JAK2 inhibition in murine systemic lupus erythematosus. 2251 30