Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neutrophil is pivotal to ANCA vasculitis pathogenesis. Fever frequently complicates ANCA diseases. This study investigated the effects of short-term heat exposure on apoptosis in neutrophils that were treated with LPS, GM-CSF, IL-8, and dexamethasone. All compounds delayed apoptosis. Heat abrogated the apoptosis-delaying effect of LPS without affecting constitutive apoptosis or delayed apoptosis by GM-CSF, IL-8, or dexamethasone. The heat effect was dose dependent over the 39 to 42 degrees C range. NF-kappaB but not extracellular signal-regulated kinase, p38 mitogen-activated protein kinase (MAPK), or phosphatidylinositol 3-kinase/Akt controlled LPS-delayed apoptosis. Furthermore, LPS-induced IkappaBalpha degradation, DNA binding, and NF-kappaB-dependent gene transcription activation were abrogated by short-term heat. When core temperatures were raised to 40.5 degrees C for 30 min in mice, LPS-induced neutrophil NF-kappaB activation also was prevented. Short-term heat removed heat-shock protein 90 from the IkappaB kinase complex, resulting in failure of LPS-induced IkappaB kinase activation. Despite delayed apoptosis, ANCA antigen expression was increased in LPS-treated neutrophils. ANCA antigen increase was prevented by p38 MAPK inhibition and by heat exposure. Heat exposure did not inhibit LPS-induced p38 MAPK phosphorylation. Instead, apoptosis-mediated p38 MAPK degradation was accelerated, thereby decreasing the p38 MAPK that was available for LPS-mediated ANCA antigen upregulation. These data suggest that fever-like temperatures modulate neutrophil behavior in this disease.
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PMID:Fever-like temperatures affect neutrophil NF-kappaB signaling, apoptosis, and ANCA-antigen expression. 1659 88

To investigate the associations of IkappaBalpha gene polymorphisms with the development and clinical manifestations of systemic lupus erythematosus (SLE), 110 patients with SLE and 120 unrelated healthy controls were enrolled in this study. The IkappaBalpha -881 A/G, -826 C/T, -550 A/T, -519 C/T, and -297 C/T polymorphisms were determined by the polymerase chain reaction/reaction fragment length polymorphism method. The genotype frequency of IkappaBalpha -826 C/T in the patients with SLE was significantly higher than that of the controls (p = 0.003, OR = 2.2, 95% CI = 1.3-3.9). The SLE patients also have significantly higher carriage rate of IkappaBalpha -826 T than the controls (p = 0.01, OR = 2.0, 95% CI = 1.2-3.4). We also found that the estimated haplotype frequency of IkappaBalpha -881A -826T -550A -519C -297C was significantly increased in the patients with SLE in comparison with that of the controls. This study also demonstrated that the association of IkappaBalpha -826 T with SLE was independent of HLA-DR15, which is associated with susceptibility to SLE in Taiwan. Moreover, a synergistic effect could also be found between IkappaBalpha -826 T and HLA-DR15. IkappaBalpha -826 T is associated with the development of SLE in Taiwan. The IkappaBalpha -881A -826T -550A -519C -297C haplotype is also associated with susceptibility to SLE. This study also demonstrated that IkappaBalpha -881G was associated with the occurrence of vasculitis in SLE patients. IkappaBalpha -550T might be a protective factor for the development of malar rash.
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PMID:I kappa B alpha promoter polymorphisms in patients with systemic lupus erythematosus. 1807 80

Impaired host defenses and vascular dysfunction are hallmarks of the late, antibiotic-refractory stages of systemic anthrax infection. Anthrax lethal toxin (LT), a key virulence factor of Bacillus anthracis, was previously shown to enhance VCAM-1 expression on primary human endothelial cells suggesting a causative link between dysregulated adhesion molecule expression and the poor immune response and vasculitis associated with anthrax. In this study, we report that LT amplification of TNF-induced VCAM-1 expression is driven transcriptionally by the cooperative activation of NF-kappaB and IFN regulatory factor-1 (IRF-1). LT enhancement of NF-kappaB phosphorylation and nuclear translocation correlated temporally with a delayed reaccumulation of IkappaBalpha, while increased induction of IRF-1 was linked to STAT1 activation. LT failed to augment TNF-induced ICAM-1 or E-selectin expression, two adhesion molecules regulated by NF-kappaB, but not IRF-1. These results suggest that LT can differentially modulate NF-kappaB target genes and highlight the importance of IRF-1 in VCAM-1 enhancement. Altering the activity of key transcription factors involved in host response to infection may be a critical mechanism by which LT contributes to anthrax pathogenesis.
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PMID:Anthrax lethal toxin enhances TNF-induced endothelial VCAM-1 expression via an IFN regulatory factor-1-dependent mechanism. 1849 Jul 52