Short Term Hyperthermia Prevents Activation of Proinflammatory Genes in Type B Synoviocytes by Blocking the Activation of the Transcription Factor NF-κB

The aim of this study was to investigate the effect and mechanisms of short term hyperthermia on a series of proinflammatory genes in type-B-synoviocytes (fibroblast like synoviocytes - FLS). In vitro experiments demonstrate that exposure of FLS to elevated temperatures for the duration of 30 minutes prevents activation of a series of genes with proinflammatory properties. Exposure to hyperthermia reduces IL-1f3 induced PGE2 release, suppresses activation of the adhesion molecules VCAM-1, ICAM-1, the cytokines TNFa, IL-1a, IL-1p, IL-8 as well as COX-2 protein synthesis. Real time RT-PCR showed that hyperthermia altered gene expression at the transcriptional level. As to the mechanism of inhibition, EMSA experiments demonstrated that exposure of FLS to hyperthermia prevents IL-1f3 induced NF-κB translocation and subsequent DNA binding. Many mechanisms have been shown to be involved in hyperthermia mediated effects on NF-κB-DNA interactions. We demonstrated by Western blot experiments that in FLS, hyperthermia prevents the phosphorylation and subsequent degradation of IκBCC, therefore retaining the NF-κB complex in the cytoplasm. Such data might, at least in part, explain and provide a rationale for treating inflammation e.g. associated with rheumatoid arthritis by balneological means.