The skin is known to be the largest organ in human organism creating interface with outer environment. The skin provides protective barrier against pathogens, physical and chemical insults, and against uncontrolled loss of water. The barrier function was primarily attributed to the stratum corneum (SC) but recent studies confirmed that epidermal tight junctions (TJs) also play important role in maintaining barrier properties of the skin. Independent observations indicate that barrier function and its recovery is impaired in aged skin. However, trans-epidermal water loss (TEWL) values remains rather unchanged in elderly population. UV radiation as major factor of photoageing impairs TJ proteins, but TJs have great self-regenerative potential. Since it may be possible that TJs can compensate TEWL in elderly due to its regenerative and compensatory capabilities, important question remains to be answered: how are TJs regulated during skin ageing? This review provides an insight into TJs functioning as epidermal barrier and summarizes current knowledge about the impact of ageing on the barrier function of the skin and epidermal TJs.
- MeSH
- epidermis metabolismus patologie účinky záření MeSH
- kožní absorpce MeSH
- lidé MeSH
- permeabilita MeSH
- perspiratio insensibilis MeSH
- stárnutí kůže * účinky záření MeSH
- stárnutí metabolismus patologie MeSH
- těsný spoj metabolismus patologie účinky záření MeSH
- ultrafialové záření škodlivé účinky MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Tumor cells interact with blood constituents and these interactions promote metastasis. Selectins are vascular receptors facilitating interactions of tumor cells with platelets, leukocytes, and endothelium, but the role of endothelial E-selectin remains unclear. Here we show that E-selectin is a major receptor for monocyte recruitment to tumor cell-activated endothelium. Experimental and spontaneous lung metastasis using murine tumor cells, without E-selectin ligands, were attenuated in E-selectin-deficient mice. Tumor cell-derived CCL2 promoted endothelial activation, resulting in enhanced endothelial E-selectin expression. The recruitment of inflammatory monocytes to metastasizing tumor cells was dependent on the local endothelial activation and the presence of E-selectin. Monocytes promoted transendothelial migration of tumor cells through the induction of E-selectin-dependent endothelial retractions and a subsequent modulation of tight junctions through dephosphorylation of VE-cadherin. Thus, endothelial E-selectin shapes the tumor microenvironment through the recruitment, adhesion, and activation of monocytes that facilitate tumor cell extravasation and thereby metastasis. These findings provide evidence that endothelial E-selectin is a novel factor contributing to endothelial retraction required for efficient lung metastasis. Cancer Res; 76(18); 5302-12. ©2016 AACR.
- MeSH
- CD antigeny metabolismus MeSH
- cévní endotel metabolismus MeSH
- E-selektin metabolismus MeSH
- endoteliální buňky metabolismus MeSH
- imunoblotting MeSH
- imunoprecipitace MeSH
- invazivní růst nádoru patologie MeSH
- kadheriny metabolismus MeSH
- modely nemocí na zvířatech MeSH
- monocyty metabolismus MeSH
- mutantní kmeny myší MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- polymerázová řetězová reakce MeSH
- průtoková cytometrie MeSH
- těsný spoj metabolismus patologie MeSH
- transendoteliální a transepiteliální migrace fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Focal cerebral contusion can be dynamic and expansive. It has been proved that subsequent expansive contusion is caused by brain parenchyma damage, especially BBB damage. We investigated a group of patients with traumatic brain injury. The patients (n=18) were divided into group I (n=7) of patients submitted to neurosurgery due to expansive contusion, and group II (n=11) of patients without surgery. Serum concentrations of NSE and S-100B protein were measured by electrochemiluminescence immunoassay, interleukin-6 (IL-6) was measured by chemiluminescent sequential immunometric assay and matrix metalloproteinases (MMP-9, MMP-2) were measured by immunoassays. Cortical biopsy specimens of brain were investigated by electron microscopy in patients with trauma brain injury submitted to neurosurgery. Biochemical investigation from first day up to third day after traumatic brain injury proved increased values of IL-6 (302.2+/-119.9 vs. 59.6+/-11.9 ng/l, p<0.02) and S-100B protein (3.064+/-1.064 vs. 0.649+/-0.182 microg/l, p<0.05) in patients with expansive lesion compared to patients without expansive contusion. Significantly higher levels of MMP-9 (150.4+/-28.46 vs. 74.11+/-13.16 ng/l, p<0.05) and of MMP-2 (814.5+/-126.3 vs. 523.1+/-25.28 ng/l, p<0.05) were found during first 3 days after admission in group I compared to group II. MMP-9 has also elevated in group II from lower values after admission (74.11+/-13.16 ng/l) up to high levels on the 10th day of hospitalization (225.1+/-49.35 ng/l). Ultrastructural investigation of endothelial cells and surrounded tissue revealed perivascular hemorrhage, increased pinocytic activity of endothelial cells, and cytotoxic edema of astroglial cells. Multivesical bodies were disclosed inside the endothelial cells. Higher levels of serum protein S-100B and IL-6 correlated with ultrastructural changes of endothelial cells, and with inflammatory response following TBI, respectively.
- MeSH
- astrocyty patologie ultrastruktura MeSH
- biologické markery krev MeSH
- biopsie MeSH
- elektronová mikroskopie MeSH
- encefalitida imunologie patologie MeSH
- endoteliální buňky patologie ultrastruktura MeSH
- financování organizované MeSH
- hematoencefalická bariéra imunologie metabolismus patologie MeSH
- interleukin-6 krev MeSH
- lidé MeSH
- neurotrofní faktory krev MeSH
- poranění mozku imunologie metabolismus patologie MeSH
- proteiny S100 krev MeSH
- těsný spoj patologie ultrastruktura MeSH
- Check Tag
- lidé MeSH
