OBJECTIVES: The S100A4 protein is known as a metastasis promoting factor; however, its involvement in non-malignant diseases such as RA and psoriasis has been recently described. The aim of this study was to investigate the expression and possible role of S100A4 in idiopathic inflammatory myopathies. METHODS: S100A4 protein expression was detected by immunohistochemistry in muscle tissue from control individuals (n = 11) and patients with PM and DM (n = 8/6). IF staining was used to co-localize S100A4 with selected cells. Cytokine expression and protein synthesis in S100A4-treated cells were analysed by RT-PCR and ELISA. RESULTS: S100A4 protein was significantly up-regulated in muscle tissue of patients with inflammatory myopathies compared with control individuals and was associated particularly with the presence of mononuclear infiltrates. Only few regenerating muscle fibres in PM/DM expressed S100A4. Then we analysed the effect of S100A4 on human myocytes and peripheral blood mononuclear cells (PBMCs). Although S100A4 did not affect myocytes, stimulation of PBMCs with S100A4 significantly induced the expression and synthesis of TNF-α, IL-1β and IL-6, but not of IFN-α. We showed that S100A4 is not directly involved in perforin/granzyme B-induced apoptosis and that it does not modulate the expression of Bax and Bcl2 mRNA in myocytes and PBMCs. CONCLUSION: Increased expression of S100A4 in inflamed muscle tissue highlights its potential role in the pathogenesis of inflammatory myopathies. S100A4 may act as a cytokine-like factor indirectly promoting muscle fibre damage by stimulating mononuclear cells to increase the synthesis of pro-inflammatory cytokines.

• MeSH
• biologické markery metabolismus   MeSH
• cytokiny genetika   metabolismus   MeSH
• dermatomyozitida genetika   metabolismus   patologie   MeSH
• dospělí MeSH
• exprese genu MeSH
• kosterní svalová vlákna účinky léků   metabolismus   patologie   MeSH
• kosterní svaly metabolismus   patologie   MeSH
• leukocyty mononukleární účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• messenger RNA metabolismus   MeSH
• polymyozitida genetika   metabolismus   patologie   MeSH
• proteiny S100 genetika   metabolismus   farmakologie   MeSH
• rekombinantní proteiny farmakologie   MeSH
• senioři MeSH
• upregulace účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: To evaluate the association between metastasis-inducing protein S100A4 and disease activity in patients with RA, and to demonstrate the effect of TNF-alpha blocking therapy on plasma levels of S100A4 in these patients. METHODS: Plasma levels of the S100A4 protein were analysed in 40 anti-TNF-alpha naive patients with active RA. Of the 40 patients, 25 were treated with adalimumab and monitored over time. The conformational form of S100A4 was analysed using size-exclusion gel chromatography. TNF-alpha mRNA expression and protein synthesis were analysed by RT-PCR and ELISA, respectively. RESULTS: Baseline levels of S100A4 were significantly correlated with disease activity in RA patients (r = 0.41; P < 0.01). After 12 weeks of treatment with adalimumab, there was an obvious shift in the conformations of S100A4 from the multimeric to the dimeric forms, whereas the total levels of the S100A4 protein remained unchanged. This suggests that the bioactive (multimer) S100A4 may decline in response to successful treatment with adalimumab. In addition, we showed significant up-regulation of TNF-alpha mRNA (P < 0.01), and protein release to the cell culture medium of monocytes stimulated with the S100A4 multimer compared with those treated with the dimer and to the unstimulated monocytes (P < 0.001). CONCLUSIONS: This is the first study to show that the levels of the S100A4 protein are correlated with RA disease activity. Furthermore, only the bioactive form, but not the total amount of S100A4, decreases after successful TNF-alpha blocking therapy in patients with RA. These data support an important role for the S100A4 multimer in the pathogenesis of RA.

• MeSH
• antirevmatika terapeutické užití   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• monocyty imunologie   účinky léků   MeSH
• monoklonální protilátky terapeutické užití   MeSH
• polymerázová řetězová reakce s reverzní transkripcí metody   MeSH
• proteiny S100 farmakologie   krev   MeSH
• revmatoidní artritida farmakoterapie   krev   MeSH
• stupeň závažnosti nemoci MeSH
• TNF-alfa antagonisté a inhibitory   biosyntéza   genetika   MeSH
• upregulace imunologie   účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH