Communications and Publications

Vol 18 n° 4

Short term hyperthermia prevents activation of proinflammatory genes in type B synoviocytes by blocking the activation of the transcription factor NF-k B

Marica Markovic
Institute of Medical Biochemistry, Clinical Centre of Serbia,Videgradska 26, 11 000 Belgrade, Serbia, markovic.marica@gmail.com

Abstract
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‑1binduced PGE2 release, suppresses activation of the adhesion molecules VCAM-1, ICAM-1, the cytokines TNFa, IL-1a, IL-1b, 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-1binduced NF-kB translocation and subsequent DNA binding. Many mechanisms have been shown to be involved in hyperthermia mediated effects on NF-kB-DNA interactions. We demonstrated by Western blot experiments that in FLS, hyperthermia prevents the phosphorylation and subsequent degradation of IkBa, therefore retaining the NF-kB 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.

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