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Regulatory effects of 1,25-dihydroxyvitamin D3 on vascular smooth muscle cells

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Tukaj S., Trzonkowski P., Tukaj C.

Acta Biochimica Polonica

2012

vol. 59

issue 3

395-400

Inflammatory response has been recognized as a central feature in the development and progression of atherosclerosis, and VSMCs (Vascular Smooth Muscle Cells) - the main cellular component of media, play an important role in this process. Many reports indicate that the biologically active vitamin D metabolite - 1,25-dihydroxyvitamin D3 (1,25(OH)2D3 = calcitriol), besides its well established role in calcium homeostasis, plays an essential role in the regulation of the inflammation process. The aim of this study was to determine the regulatory effects of calcitriol, applied at two supra-physiological doses (10 nM and 100 nM), in VSMC culture. Secretion of the pro-inflammatory cytokines, IL-6 and TNF-α, was significantly attenuated in calcitriol-treated VSMC culture, but the level of anti-inflammatory TGF-β was generally unchanged. Since in advanced atherosclerosis lesions several cell types, including VSMCs, overproduce the HSP70 chaperone protein, we also checked the effects of calcitriol on its synthesis. The presence of 1,25(OH)2D3 did not affect HSP70 synthesis under physiological conditions but the synthesis of HSP70 in VSMCs exposed to heat shock was significantly inhibited by calcitriol (=100 nM). We observed that 1,25(OH)2D3 induced SOD 1 activity, stimulated the expression of IκB-α, and did not influence the level of NF-κB-p65 in VSMCs. The results of our study suggest that 1,25(OH)2D3 may serve as a natural anti-inflammatory agent and may therefore play a beneficial role in the physiology of VSMC in some contexts of atherosclerosis.

Cytokines of the Th1 and Th2 type in sera of rheumatoid arthritis patients; correlations with anti-Hsp40 immune response and diagnostic markers

76%

Tukaj S., Kotlarz A., Jóźwik A., Smoleńska Ż., Bryl E., Witkowski J. M., Lipińska B.

Acta Biochimica Polonica

2010

vol. 57

issue 3

327-332

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.

Vitamin D status in patients with rheumatoid arthritis: a correlation analysis with disease activity and progression, as well as serum IL-6 levels

76%

Polasik K., Piotrowska E., Lipińska B., Witkowski J., Bryl E., Tukaj S.

Acta Biochimica Polonica

2017

vol. 64

issue 4

667-670

Objectives. Recent epidemiological studies suggested an association between a poor vitamin D [25(OH)D] status, inflammatory mediators, and rheumatoid arthritis (RA). We have recently proposed that pro-inflammatory interleukin 6 (IL-6) may represent a good marker for disease activity of RA. The aim of this study was to investigate the relationship between serum 25(OH)D levels and disease activity, joint damage, as well as serum IL-6 levels in a Polish RA population. Materials and Methods. Serum 25(OH)D levels were measured in 35 female RA patients and 38 age- and gender-matched healthy controls. Statistical correlations between 25(OH)D levels and the disease activity score 28 (DAS 28), joint damage based on the Steinbrocker criteria, as well as serum IL-6 levels were performed. Results. There was no statistically significant difference between levels of 25(OH)D in RA (16.89±8.57 ng/ml) and healthy controls (14.12±7.51 ng/ml), and the vitamin D deficiency (<20 ng/ml) was found in 71.43% of RA patients and 73.68 % of healthy controls. While vitamin D status did not correlate with DAS 28 (r=0.265, p=0.149) and joint damage based on the Steinbrocker criteria (r=0.367, p=0.065), a positive correlation between 25(OH)D and IL-6 (r=0.537, p=0.002) was observed in RA. Conclusion. Although further studies on a larger group of patients will be needed to confirm the data presented here, it seems that hypovitaminosis D is common in the RA patients and middle-aged non-RA healthy women in the Polish population. 25(OH)D levels were similar in the RA patients and age- and gender-matched healthy controls, and were not associated with joint damage and disease activity in patients.

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3 Acta Biochimica Polonica

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3 Tukaj S.

2 Bryl E.

2 Lipińska B.

1 Jóźwik A.

1 Kotlarz A.

1 Piotrowska E.

1 Polasik K.

1 Smoleńska Ż.

1 Trzonkowski P.

1 Tukaj C.

1 Witkowski J.

1 Witkowski J. M.

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Regulatory effects of 1,25-dihydroxyvitamin D3 on vascular smooth muscle cells

Cytokines of the Th1 and Th2 type in sera of rheumatoid arthritis patients; correlations with anti-Hsp40 immune response and diagnostic markers

Vitamin D status in patients with rheumatoid arthritis: a correlation analysis with disease activity and progression, as well as serum IL-6 levels