Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis. The longitudinal analysis comprised 30 patients with SSc associated interstitial lung disease (ILD) routinely treated with cyclophosphamide. Hsp90 was increased in SSc compared to healthy controls. Hsp90 correlated positively with C-reactive protein and negatively with pulmonary function tests: forced vital capacity and diffusing capacity for carbon monoxide (DLCO). In patients with diffuse cutaneous (dc) SSc, Hsp90 positively correlated with the modified Rodnan skin score. In SSc-ILD patients treated with cyclophosphamide, no differences in Hsp90 were found between baseline and after 1, 6, or 12 months of therapy. However, baseline Hsp90 predicts the 12-month change in DLCO. This study shows that Hsp90 plasma levels are increased in SSc patients compared to age-/sex-matched healthy controls. Elevated Hsp90 in SSc is associated with increased inflammatory activity, worse lung functions, and in dcSSc, with the extent of skin involvement. Baseline plasma Hsp90 predicts the 12-month change in DLCO in SSc-ILD patients treated with cyclophosphamide.

• MeSH
• C-reaktivní protein metabolismus   MeSH
• cyklofosfamid terapeutické užití   MeSH
• dermatitida metabolismus   MeSH
• difuzní kapacita plic účinky léků   MeSH
• dospělí MeSH
• imunosupresiva terapeutické užití   MeSH
• intersticiální plicní nemoci krev   farmakoterapie   etiologie   MeSH
• kůže patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• oxid uhelnatý metabolismus   MeSH
• plíce patofyziologie   MeSH
• prospektivní studie MeSH
• proteiny tepelného šoku HSP90 krev   MeSH
• průřezové studie MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• systémová sklerodermie krev   komplikace   farmakoterapie   MeSH
• vitální kapacita 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

Fibronectin (FN) circulating in the blood and produced by cells provides the basis of the extracellular matrix (ECM) formed in healing acute wounds. The time-dependent deposition of FN by macrophages, its synthesis by fibroblasts and myofibroblasts, and later degradation in the remodeled granulation tissue are a prerequisite for successful healing of wounds. However, the pattern of FN expression and deposition in skin lesions is disturbed. The degradation of the ECM components including FN in varicose veins prevails over ECM synthesis and deposition. FN is inconspicuous in the fibrotic lesions in lipodermatosclerosis, while tenascin-C containing FN-like peptide sequences are prominent. FN is produced in large amounts by fibroblasts at the edge of venous ulcers but FN deposition at the wound bed is impaired. Both the proteolytic environment in the wounds and the changed function of the ulcer fibroblasts may be responsible for the poor healing of venous ulcers. The aim of this review is to describe the current knowledge of FN pathophysiology in chronic venous diseases. In view of the fact that FN plays a crucial role in organizing the ECM, further research focused on FN metabolism in venous diseases may bring results applicable to the treatment of the diseases.

• MeSH
• chronická nemoc MeSH
• dermatitida metabolismus   patologie   MeSH
• fibronektiny metabolismus   MeSH
• lidé MeSH
• lokalizovaná sklerodermie metabolismus   patologie   MeSH
• signální transdukce MeSH
• varixy metabolismus   patologie   patofyziologie   MeSH
• vény metabolismus   patologie   patofyziologie   MeSH
• žilní insuficience metabolismus   patologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

In this study, we compared selected silymarin components, such as quercetin (QE), 2,3-dehydrosilybin (DHS) and silybin (SB), with the anti-inflammatory drug indomethacin (IND) in terms of their wound healing potential. In view of the fact that pathological cutaneous wound healing is associated with persistent inflammation, we studied their anti-inflammatory activity against inflammation induced by bacterial lipopolysaccharide (LPS). We investigated the regulation of crucial pro-inflammatory transcription factors-nuclear factor kappa-B (NF-κB) and activator protein 1 (AP-1)-as well as the expression of downstream inflammatory targets by Western blotting, real-time PCR (RT-PCR), electrophoretic mobility shift assay (EMSA), and/or enzyme-linked immunosorbent assay (ELISA) in vitro using primary normal human dermal fibroblasts (NHDF). We demonstrated the greater ability of DHS to modulate the pro-inflammatory cytokines production via the NF-κB and AP-1 signaling pathways when compared to other tested substances. The prolonged exposure of LPS-challenged human dermal fibroblasts to DHS had both beneficial and detrimental consequences. DHS diminished interleukin-6 (IL-6) and interleukin-8 (IL-8) secretion but induced the significant upregulation of IL-8 mRNA associated with NF-κB and AP-1 activation. The observed conflicting results may compromise the main expected benefit, which is the acceleration of the healing of the wound via a diminished inflammation.

• MeSH
• antiflogistika farmakologie   MeSH
• chemokiny metabolismus   MeSH
• cytokiny metabolismus   MeSH
• dermatitida farmakoterapie   genetika   metabolismus   patologie   MeSH
• exprese genu MeSH
• fibroblasty účinky léků   metabolismus   MeSH
• hojení ran účinky léků   MeSH
• lidé MeSH
• lipopolysacharidy imunologie   MeSH
• messenger RNA genetika   metabolismus   MeSH
• NF-kappa B metabolismus   MeSH
• proliferace buněk účinky léků   MeSH
• silymarin farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The epidermis is a stratified tissue composed of different keratinocyte layers that create a barrier protecting the body from external influences, pathogens, and dehydration. The barrier function is mainly achieved by its outermost layer, the stratum corneum. To create a mouse model to study pathophysiological processes in the outermost layers of the epidermis in vivo and in vitro we prepared a construct containing red fluorescent td-Tomato reporter sequence under the control of involucrin promoter and its first intron. Transgenic mice were generated by pronuclear injection and the expression and regulation of the transgene was determined by in vivo imaging and fluorescent microscopy. The promoter targeted the transgene efficiently and specifically into the outermost epidermal layers although weak expression was also found in epithelia of tongue and bladder. The regulation of expression in the epidermis, i.e. fluorescence intensity of the reporter, could be easily followed during wound healing and dermatitis. Thus, these transgenic mice carrying the tdTomato reporter could be used as a valuable tool to study impact of various genes dysregulating the epidermal barrier and to follow effects of therapeutic agents for treatment of skin diseases in vivo.

• MeSH
• buněčná diferenciace MeSH
• dermatitida metabolismus   patofyziologie   MeSH
• epidermis metabolismus   patofyziologie   MeSH
• epitel metabolismus   patofyziologie   MeSH
• fluorescenční mikroskopie MeSH
• genový targeting metody   MeSH
• hojení ran MeSH
• imunohistochemie MeSH
• introny MeSH
• jazyk metabolismus   patofyziologie   MeSH
• luminescentní proteiny metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• promotorové oblasti (genetika) MeSH
• proteinové prekurzory genetika   MeSH
• regulace genové exprese MeSH
• reportérové geny MeSH
• Solanum lycopersicum genetika   MeSH
• transgeny MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• alkalická rezistence, alkalická neutralizace,
• MeSH
• alkálie metabolismus   škodlivé účinky   MeSH
• dermatitida metabolismus   MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• kožní nemoci metabolismus   MeSH
• kůže * metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• nemoci z povolání metabolismus   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři MeSH