Advancing excellence in laboratory medicine for better healthcare worldwide

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,  

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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