Tissue Barriers最新文献

Lipids and their mediators have important regulatory functions in many cellular processes, including the innate antiviral response. The aim of this study was to compare the lipid membrane composition of in vitro differentiated primary bronchial epithelial cells (PBECs) with ex vivo bronchial brushings and to establish whether any changes in the lipid membrane composition affect antiviral defense of cells from donors without and with severe asthma. Using mass spectrometry, we showed that the lipid membrane of in vitro differentiated PBECs was deprived of polyunsaturated fatty acids (PUFAs) compared to ex vivo bronchial brushings. Supplementation of the culture medium with arachidonic acid (AA) increased the PUFA-content to more closely match the ex vivo membrane profile. Rhinovirus (RV16) infection of AA-supplemented cultures from healthy donors resulted in significantly reduced viral replication while release of inflammatory mediators and prostaglandin E2 (PGE₂) was significantly increased. Indomethacin, an inhibitor of prostaglandin-endoperoxide synthases, suppressed RV16-induced PGE₂ release and significantly reduced CXCL-8/IL-8 release from AA-supplemented cultures indicating a link between PGE₂ and CXCL8/IL-8 release. In contrast, in AA-supplemented cultures from severe asthmatic donors, viral replication was enhanced whereas PTGS2 expression and PGE₂ release were unchanged and CXCL8/IL-8 was significantly reduced in response to RV16 infection. While the PTGS2/COX-2 pathway is initially pro-inflammatory, its downstream products can promote symptom resolution. Thus, reduced PGE₂ release during an RV-induced severe asthma exacerbation may lead to prolonged symptoms and slower recovery. Our data highlight the importance of reflecting the in vivo lipid profile in in vitro cell cultures for mechanistic studies.

Gut-vascular barrier (GVB) is the second barrier in mucosa to control systemic dissemination of gut bacteria. Severe burns induce enteroglial cells to produce S100B and endothelial cells to generate ADAM10 and cause vitamin D3 insufficiency/deficiency and GVB disruption. It is not clear whether vitamin D3 supplementation attenuates GVB damage via regulation of S100B/ADAM10 pathway. Here, GVB disruption was induced by 30% of total body surface area scalds. Rats were treated with 1,25(OH)2D3 (0.05, 0.5 or 5 μg/kg) or S100B monoclonal antibody (S100BmAb, 10 μg/kg) or GI254023X (ADAM10 inhibitor, 100 mg/kg). Rat enteric glial cell-line CRL2690 and rat intestinal microvascular endothelial cells (RIMECs) were treated with S100B (5 μM) or plus 1,25(OH)2D3 (0.05, 0.5 or 5 μM) or GI254023X (5 μM). S100B, TNF-α, 25(OH)D3 and 1,25(OH)2D3 in serum and gut mucosa were determined by enzyme-linked immunosorbent assay. The endothelial permeability was measured using FITC-dextran 70 kDa. ADAM10 and β-catenin expression was assayed by Western blot. The results showed that 1,25(OH)2D3 and 25(OH)D3 concentration in serum reduced whereas TNF-α and S100B in serum and gut mucosa increased in burned rats. S100BmAb, GI254023X and 1,25(OH)2D3 treatment lowered burns-increased GVB permeability. 1,25(OH)2D3 also decreased S100B concentration in serum and gut mucosa. 1,25(OH)2D3 inhibited S100B release from TNF-α-treated CRL2690 and raised β-catenin while decreasing ADAM10 protein in S100B-treated RIMECs. 1,25(OH)2D3 and GI254023X also decreased the endothelial permeability of S100B-treated RIMECs. Collectively, these findings provide evidence that severe burns lower serum 25(OH)D3 and 1,25(OH)2D3 concentration. 1,25(OH)2D3 supplementation alleviates burns-elicited GVB disruption via inhibition of S100B/ADAM10 signaling.

Although the majority of the population will be protected due to the advent and widespread use of the HPV vaccine, the treatment of cervical cancer for all causes, including HPV-negative cervical cancer, is still worthy of further research. The focal point of this study was Canadine's inhibition of epithelial-mesenchymal transformation (EMT) in cervical cancer. Immunoblotting, wound healing and tumor invasion experiments showed that low concentration of Canadine could inhibit the EMT process, proliferation and migration of HT-3 cells (HPV-negative cell line). Combined with GEO database, it was found that the expression levels of several genes highly expressed in cervical tumor tissues could be inhibited by Canadine, especially MAGEA3. Further experiments confirmed that the inhibition of Canadine on MAGEA3 protein increased with time. The small interference and overexpression plasmid of MAGEA3 were designed and verified. In HT-3 cells, when MAGEA3 levels were directly decreased, mesenchymal phenotypic markers were decreased and epithelial phenotypic markers were increased. The opposite result was obtained by overexpression of MAGEA3. In addition, the inhibition of EMT due to the reduction of endogenous MAGEA3 by Canadine was also offset by the overexpression of exogenous MAGEA3. The study concludes that Canadine inhibits EMT of cervical cancer by inhibiting MAGEA3.

NAFLD is a condition that develops when the liver accumulates excess fat without alcohol consumption. This chronic liver ailment progresses along with insulin resistant and is typically not diagnosed until the patients have cirrhosis. Nuclear hormone receptor superfamily PPARs are essential for metabolism of fatty acids and glucose. In liver, lipid metabolism is regulated by nuclear receptors and PPARα, and PPARβ/δ encourages fatty acid β-oxidation. PPAR-γ, an energy-balanced receptor is a crucial regulator in NAFLD. The partial activation of PPAR-γ could lead to increased level of adiponectin and insulin sensitivity, thus improved NAFLD. Because of less side effects, natural compounds are emerged as potential therapeutic agents for NAFLD by PPARγ agonists. Although the results from preclinical studies are promising, further research is needed to determine the potential dosing and efficacy of mentioned compounds in human subjects. In this review, we summarize the effect of natural PPARγ agonist in the NAFLD.

The epidermis of the skin provides a barrier between the organism and the external environment. It is constantly subjected to physical and chemical insults, and thus susceptible to wounding and to neoplastic transformation. Long-lasting epigenetic modifications in epidermal stem cells are now shown to link responses to skin injuries with cell priming for carcinoma development, through regulation of histone H2A ubiquitylation.

Sertoli cells are a crucial component of the blood-testis barrier (BTB), which isolates the adluminal compartment of the seminiferous tubules from the rest of the testis thus forming an environment to immunely protect the developing germ cells. The mechanisms of regulating immune responses within this environment are currently under investigation. Here, we focused on Sertoli cell regulation of the complement system.

The rising prevalence of fungal infections is a significant and growing public health threat, and this risk is further underscored by our incomplete understanding of why organs like the kidney are so susceptible to systemic candidiasis. To combat the high mortality of such infections, we urgently need to advance our understanding of fungal pathogenesis and how it articulates with human immune response. Now, a recent landmark study has illuminated a crucial role of the complement system in the response to candidiasis and determined the stepwise local response of phagocytes within the kidney during infection. These fundamental discoveries provide crucial insights that can be leveraged to improve the care and outcome for patients with fungal infections.

Sertoli cells are unique cells that contribute to the formation of the blood-testis barrier, which is important in sustaining the environment to promote spermatogenesis and to protect immunogenic germ cells from autoimmune destruction. This is achieved through tight junctions and production of regulatory immune factors. These Sertoli cell attributes make them a relevant model for various studies involving male reproduction, autoimmune protection, and even transplantation. RNA sequencing analyses were performed on baseline neonatal porcine Sertoli cells (NPSC) and NPSC after incubation in normal human serum for 90 minutes. We previously analyzed this data for immune-related factors, such as complement components, and for differentially expressed genes related to immune function. Still, these data sets provide insight into understanding how Sertoli cells create an immunoregulatory environment, which has applications in reproduction, transplantation, and autoimmunity.

The microbiome is a keystone of adult gastrointestinal (GI) tract health, where it facilitates digestion, wards off pathogen colonization, and exerts a powerful influence on the physiological health of organs ranging from the brain to the kidneys. From its establishment at birth and through the initial years of childhood, the human microbiome is particularly dynamic, shifting in its composition and alpha (species) diversity to an adult profile as dietary sustenance transitions from milk-based sources to others such as solid food. An innovative study has now demonstrated how microbiome maturation is requisite both for the progression of immune system development and for long-term gut barrier function. These insights have significant ramifications for designing pediatric approaches to cultivate immune cell ontogeny in the formative stages of human infancy.

Blood barriers serve as key points of transport for essential molecules as well as lines of defense to protect against toxins. In vitro modeling of these barriers is common practice in the study of their physiology and related diseases. This review describes a common method of using an adaptable, low cost, semipermeable, suspended membrane to experimentally model three blood barriers in the human body: the blood-brain barrier (BBB), the gut-blood barrier (GBB), and the air-blood barrier (ABB). The GBB and ABB both protect from the outside environment, while the BBB protects the central nervous system from potential neurotoxic agents in the blood. These barriers share several commonalities, including the formation of tight junctions, polarized cellular monolayers, and circulatory system contact. Cell architectures used to mimic barrier anatomy as well as applications to study function, dysfunction, and response provide an overview of the versatility enabled by these cultural systems.