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Fever-like temperatures affect neutrophil NF-kappaB signaling, apoptosis, and ANCA-antigen expression

Item Type:Article
Title:Fever-like temperatures affect neutrophil NF-kappaB signaling, apoptosis, and ANCA-antigen expression
Creators Name:Kettritz, R. and Choi, M. and Salanova, B. and Wellner, M. and Rolle, S. and Luft, F.C.
Abstract: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°C range. NF-κB but not extracellular signal-regulated kinase, p38 mitogen-activated protein kinase (MAPK), or phosphatidylinositol 3-kinase/Akt controlled LPS-delayed apoptosis. Furthermore, LPS-induced IκBα degradation, DNA binding, and NF-κB- dependent gene transcription activation were abrogated by short-term heat. When core temperatures were raised to 40.5°C for 30 min in mice, LPS-induced neutrophil NF-κB activation also was prevented. Short-term heat removed heat-shock protein 90 from the IκB kinase complex, resulting in failure of LPS-induced IκB 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.
Keywords:Antigens, Antineutrophil Cytoplasmic Antibodies, Apoptosis, Body Temperature, Cultured Cells, Fever, Hot Temperature, Inbred C57BL Mice, NF-kappa B, Neutrophil Activation, Neutrophils, Signal Transduction, Vasculitis, Animals, Mice
Source:Journal of the American Society of Nephrology
Publisher:American Society of Nephrology
Page Range:1345-1353
Date:May 2006
Official Publication:https://doi.org/10.1681/ASN.2005090948
PubMed:View item in PubMed

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