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Conventional calpains and programmed cell death

100%
Łopatniuk P., Witkowski J. M.
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2011
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vol. 58
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issue 3
287-296
EN
The evidence on the crucial role of a family of calcium-dependent cysteine proteases called calpains in programmed cell death is rich and still growing. However, understanding of the mechanisms of their functions in apoptosis is not full yet. Calpains have been implicated in both physiological and pathological cell death control, especially in various malignancies, but also in the immune system development and function. There is also growing evidence on calpain involvement in apoptosis execution in certain pathological conditions of the central nervous system, in cardiovascular diseases, etc. Understanding of the clinical significance of calpain activation pathways, after intense studies of the influence of calpain activity on drug-induced apoptosis, seems especially important lately, as calpains have become noticed as potential therapeutic targets. To allow pharmacological targeting of these enzymes, thorough knowledge of their patterns of activation and further interactions with already known apoptotic pathways is necessary. A comprehensive summary of both well established and recently obtained information in the field is an important step that may lead to future advances in the use of calpain-targeted agents in the clinic.
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Cytokines of the Th1 and Th2 type in sera of rheumatoid arthritis patients; correlations with anti-Hsp40 immune response and diagnostic markers

61%
Tukaj S., Kotlarz A., Jóźwik A., Smoleńska Ż., Bryl E., Witkowski J. M., Lipińska B.
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2010
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vol. 57
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issue 3
327-332
EN
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease which affects approximately 1% of the population worldwide. Recent research on the role of heat shock proteins (Hsps) in RA development indicates that they may have pro- or anti-inflammatory effect, most probably via modulating cytokine secretion. We investigated type Th1 (INFγ, TNFα, IL-2) and type Th2 (IL-10, IL-6, IL-4) cytokine levels in sera of RA patients and healthy controls, using flow cytometric bead array assay, and searched for correlations between the cytokine levels and serum antibodies against bacterial (DnaJ) and human (Hdj1, Hdj2 and Hdj3) Hsp40 proteins, as well as clinical and laboratory parameters. The levels of all cytokines studied were significantly increased in RA patients; the highest increase relative to healthy controls (7-fold) was observed for IL-6 and its levels correlated positively with the antibodies directed to DnaJ and to the C-terminal domain of Hdj2, and with diagnostic parameters (DAS 28, Steinbrocker RTG criteria, ARA/7, ESR, TEN, SW and GH). INFγ levels correlated negatively with DAS 28, ESR, TEN and SW. No correlations were found for TNFα, IL-2 or IL-4. Our results support the hypothesis of Hsp40 involvement in RA as well as indicate that IL-6 serum level is a good marker of the RA activity.
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