Tissue Barriers最新文献

{"title":"Tight junctions: from molecules to gastrointestinal diseases.","authors":"Aekkacha Moonwiriyakit,&nbsp;Nutthapoom Pathomthongtaweechai,&nbsp;Peter R Steinhagen,&nbsp;Papasara Chantawichitwong,&nbsp;Wilasinee Satianrapapong,&nbsp;Pawin Pongkorpsakol","doi":"10.1080/21688370.2022.2077620","DOIUrl":"https://doi.org/10.1080/21688370.2022.2077620","url":null,"abstract":"<p><p>Intestinal epithelium functions as a tissue barrier to prevent interaction between the internal compartment and the external milieu. Intestinal barrier function also determines epithelial polarity for the absorption of nutrients and the secretion of waste products. These vital functions require strong integrity of tight junction proteins. In fact, intestinal tight junctions that seal the paracellular space can restrict mucosal-to-serosal transport of hostile luminal contents. Tight junctions can form both an absolute barrier and a paracellular ion channel. Although defective tight junctions potentially lead to compromised intestinal barrier and the development and progression of gastrointestinal (GI) diseases, no FDA-approved therapies that recover the epithelial tight junction barrier are currently available in clinical practice. Here, we discuss the impacts and regulatory mechanisms of tight junction disruption in the gut and related diseases. We also provide an overview of potential therapeutic targets to restore the epithelial tight junction barrier in the GI tract.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":"11 2","pages":"2077620"},"PeriodicalIF":3.1,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10161963/pdf/KTIB_11_2077620.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9689807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coenzyme Q10 protects against doxorubicin-induced cardiomyopathy via antioxidant and anti-apoptotic pathway.","authors":"Dalia A Shabaan,&nbsp;Nora Mostafa,&nbsp;Manal M El-Desoky,&nbsp;Eetmad A Arafat","doi":"10.1080/21688370.2021.2019504","DOIUrl":"https://doi.org/10.1080/21688370.2021.2019504","url":null,"abstract":"<p><p>Doxorubicin (Dox) is an anthracycline antibiotic that treats a variety of malignancies. Unfortunately, its cardiotoxicity limits its therapeutic usefulness. Coenzyme Q10 (CoQ10) has effectively treated and prevented various cardiac diseases and toxicities. This study aimed to evaluate the possible antioxidative and anti-apoptotic cardioprotective effects of CoQ10 against doxorubicin-induced histopathological and molecular changes in cardiomyocytes. Twenty-eight adult Wistar rats were divided into positive control, negative control, Dox-treated group, and Dox+CoQ10-treated. On the 16th day after the start of treatment, the hearts of all rats were dissected, and the left ventricles were processed for histological evaluation; immunohistochemical staining with caspase-3 and inducible nitric oxide synthase (iNOS); ultrastructural examination of cardiomyocytes; molecular assessment of proapoptotic gene Bax and anti-apoptotic gene expression Bcl-2; and biochemical study of malondialdehyde (MDA). The Dox-treated group had disorganized cardiomyocytes with increased interstitial space, vacuolated cytoplasm, and multiple small-sized pyknotic nuclei. A significant increase in caspase-3 and iNOS immunoexpression was observed. Ultrastructurally, the mitochondria were large with abnormal shapes, vacuolated cytoplasm, multiple vacuoles and autophagosomes, collagen fibril accumulation, and multiple small hyperchromatic nuclei. The intercalated discs were disorganized with loss of desmosome junction. The cardiomyocytes also showed significantly increased MDA levels and upregulation of Bax/Bcl-2 gene expression ratio. Co-administration of CoQ10 resulted in significant improvement in the histopathological picture, with a significant decrease in caspase-3 and iNOS immunoexpression and downregulation of the Bax/Bcl-2 gene expression ratio. In conclusion, CoQ10 protects against Dox-induced cardiotoxicity through the regulation of proapoptotic and anti-apoptotic gene expression.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":"11 1","pages":"2019504"},"PeriodicalIF":3.1,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870010/pdf/KTIB_11_2019504.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10609017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The therapeutic prospect of zinc oxide nanoparticles in experimentally induced diabetic nephropathy.","authors":"Samia A Abd El-Baset,&nbsp;Nehad F Mazen,&nbsp;Rehab S Abdul-Maksoud,&nbsp;Asmaa A A Kattaia","doi":"10.1080/21688370.2022.2069966","DOIUrl":"https://doi.org/10.1080/21688370.2022.2069966","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is the most frequent cause of end-stage renal failure. Zinc oxide nanoparticles (ZnO-NPs) are promising antidiabetic agents. Our aim was to evaluate the prospective efficacy of ZnO-NPs in treating DN in streptozotocin-induced diabetic rats. Rats were randomly dispersed into three sets: control group, DN group and DN + ZnO-NPs group. ZnO-NPs were given at a dose of 10 mg/kg/day by oral gavage for 4 weeks. Urine and blood samples were processed for biochemical analyses. Kidney samples were managed for light and electron microscopy studies. Immune histochemical staining of P53, aquaporin11 (AQP11) and mechanistic target of rapamycin (mTOR) were performed. Gene analyses of nephrin, podocin, beclin-1, LC3 and p62 were done. Administration of ZnO-NPs ameliorated the functional and histopathological alterations of the kidney in a rat model of diabetic nephropathy. ZnO-NPs retained the constancy of the glomerular filtration barrier and restored almost normal renal structure. This was confirmed by upregulation of mRNA expression of podocyte markers (nephrin and podocin) and AQP11 immune histochemical expression in the renal tubules. The beneficial outcomes of ZnO-NPs might be attributed to activation of autophagy through inhibiting mTOR signaling pathway. ZnO-NPs enhanced beclin-1 and LC3 mRNA expressions and reduced p62 mRNA expression. ZnO-NPs also exerted anti-apoptotic potential (evidenced by the decrease in p53 immune expression), anti-inflammatory and anti-oxidant effect [endorsed by suppression of serum cyclooxygenase-2 (COX-2) enzyme activity, tissue nuclear factor kappa beta (NF-κB) level and blood hypoxia-inducible factors (HIF-1α) level]. These results may point the way to an effective therapy of DN.Abbreviations: AQP11 Aquaporin11; BUN: Blood urea nitrogen; COX-2: Cyclooxygenase-2; DAB: 3, 3'-diaminobenzidine; DM: Diabetes mellitus; DN: Diabetic nephropathy; ELISA: Enzyme-linked immunosorbent assay; H&E: Hematoxylin & eosin; HIF-1α: Hypoxia-inducible factors; iNOS: inducible nitric oxide synthase; LC3: Microtubule-associated protein 1 light chain 3; mTOR: Mechanistic target of rapamycin; NF-κB: Nuclear factor kappa beta; NPs: Nanoparticles; PAS: Periodic acid Schiff; PCR: Polymerase chain reaction; PGE2: Prostaglandin E2; ROS: Reactive oxygen species; STZ: Streptozotocin; X ± SEM: Mean ± standard error of means; Zn: Zinc; ZnO-NPs: Zinc oxide nanoparticles.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":"11 1","pages":"2069966"},"PeriodicalIF":3.1,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870014/pdf/KTIB_11_2069966.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9457771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GRP75 as a functional element of cholix transcytosis.","authors":"Keyi Liu,&nbsp;Tom Hunter,&nbsp;Alistair Taverner,&nbsp;Kevin Yin,&nbsp;Julia MacKay,&nbsp;Kate Colebrook,&nbsp;Morgan Correia,&nbsp;Amandine Rapp,&nbsp;Randall J Mrsny","doi":"10.1080/21688370.2022.2039003","DOIUrl":"https://doi.org/10.1080/21688370.2022.2039003","url":null,"abstract":"<p><p>Cholix (Chx) is secreted by non-pandemic strains of <i>Vibrio cholerae</i> in the intestinal lumen. For this exotoxin to induce cell death in non-polarized cells in the intestinal lamina propria, it must traverse the epithelium in the fully intact form. We identified host cell elements in polarized enterocytes associated with Chx endocytosis and apical to basal (A→B) vesicular transcytosis. This pathway overcomes endogenous mechanisms of apical vesicle recycling and lysosomal targeting by interacting with several host cell proteins that include the 75 kDa glucose-regulated protein (GRP75). Apical endocytosis of Chx appears to involve the single membrane spanning protein TMEM132A, and interaction with furin before it engages GRP75 in apical vesicular structures. Sorting within these apical vesicles results in Chx being trafficked to the basal region of cells in association with the Lectin, Mannose Binding 1 protein LMAN1. In this location, Chx interacts with the basement membrane-specific heparan sulfate proteoglycan perlecan in recycling endosomes prior to its release from this basal vesicular compartment to enter the underlying lamina propria. While the furin and LMAN1 elements of this Chx transcytosis pathway undergo cellular redistribution that are reflective of the polarity shifts noted for coatamer complexes COPI and COPII, GRP75 and perlecan fail to show these dramatic rearrangements. Together, these data define essential steps in the A→B transcytosis pathway accessed by Chx to reach the intestinal lamina propria where it can engage and intoxicate certain non-polarized cells.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":"11 1","pages":"2039003"},"PeriodicalIF":3.1,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c6/df/KTIB_11_2039003.PMC9870019.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10599377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A host-gut microbial amino acid co-metabolite, <i>p</i>-cresol glucuronide, promotes blood-brain barrier integrity <i>in vivo</i>.","authors":"Andrew V Stachulski,&nbsp;Tobias B-A Knausenberger,&nbsp;Sita N Shah,&nbsp;Lesley Hoyles,&nbsp;Simon McArthur","doi":"10.1080/21688370.2022.2073175","DOIUrl":"https://doi.org/10.1080/21688370.2022.2073175","url":null,"abstract":"<p><p>The sequential activity of gut microbial and host processes can exert a powerful modulatory influence on dietary components, as exemplified by the metabolism of the amino acids tyrosine and phenylalanine to <i>p</i>-cresol by gut microbes, and then to <i>p</i>-cresol glucuronide (pCG) by host enzymes. Although such glucuronide conjugates are classically thought to be biologically inert, there is accumulating evidence that this may not always be the case. We investigated the activity of pCG, studying its interactions with the cerebral vasculature and the brain <i>in vitro</i> and <i>in vivo</i>. Male C57Bl/6 J mice were used to assess blood-brain barrier (BBB) permeability and whole-brain transcriptomic changes in response to pCG treatment. Effects were then further explored using the human cerebromicrovascular endothelial cell line hCMEC/D3, assessing paracellular permeability, transendothelial electrical resistance and barrier protein expression. Mice exposed to pCG showed reduced BBB permeability and significant changes in whole-brain transcriptome expression. Surprisingly, treatment of hCMEC/D3 cells with pCG had no notable effects until co-administered with bacterial lipopolysaccharide, at which point it was able to prevent the permeabilizing effects of endotoxin. Further analysis suggested that pCG acts as an antagonist at the principal lipopolysaccharide receptor TLR4. The amino acid phase II metabolic product pCG is biologically active at the BBB, antagonizing the effects of constitutively circulating lipopolysaccharide. These data add to the growing literature showing glucuronide conjugates to be more than merely metabolic waste products and highlight the complexity of gut microbe to host communication pathways underlying the gut-brain axis.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":"11 1","pages":"2073175"},"PeriodicalIF":3.1,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9177591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmigration of macrophages through primary adult rat Sertoli cells.","authors":"Hassan Kabbesh,&nbsp;Muhammad A Riaz,&nbsp;Alexandra D Jensen,&nbsp;Georgios Scheiner-Bobis,&nbsp;Lutz Konrad","doi":"10.1080/21688370.2022.2064179","DOIUrl":"https://doi.org/10.1080/21688370.2022.2064179","url":null,"abstract":"<p><p>The blood testis barrier (BTB) is often studied with isolated immature Sertoli cells (SCs), transepithelial resistance (TER) measurements and FITC dextran diffusion assays. Recently, it was found that even in the absence of SCs, only few immune cells enter the seminiferous tubules. Thus, in this study, we evaluated the testicular immunological barrier (TIB) <i>in vitro</i> by transmigration of macrophages through SCs with and without peritubular cells (PCs) and with or without matrigel (MG). Primary PCs were isolated from adult rat testis and kept in mono- or co-cultures with the conditionally reprogrammed primary adult Sertoli cell line (PASC1) from rat that has been recently generated by our group. Rat monocytes isolated from fresh blood were differentiated into M0 macrophages, and after polarization to M1 or M2 macrophages characterized by gene expression of CXCL11 and TNF-α for M1, or CCL17 and CCL22 for M2. Transmigration of LeukoTracker-labeled M0, M1, and M2 macrophages through mono- and co-cultures of PCs/SCs with and without MG demonstrated that SCs are the main constituent of the TIB <i>in vitro</i> with only a negligible contribution of PCs or MG. Moreover, M2 macrophages showed less migration activity compared to M0 or M1. Treatment of SCs with testosterone (T) showed positive effects on the barrier in contrast to negative effects by interleukin-6 (IL-6) or tumor necrosis factor-α (TNF-α). The new transmigration model is suitable to evaluate transmigration of macrophages through a barrier consisting of testicular cells and can be applied to study the integrity of testicular barriers with respect to immunological aspects.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":"11 1","pages":"2064179"},"PeriodicalIF":3.1,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870002/pdf/KTIB_11_2064179.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9683112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-activity relationship of a peptide permeation enhancer.","authors":"Joël Brunner,&nbsp;Gerrit Borchard","doi":"10.1080/21688370.2022.2060692","DOIUrl":"https://doi.org/10.1080/21688370.2022.2060692","url":null,"abstract":"<p><p>The pentapeptide L-R5 has previously been shown to transiently increase the permeability of nasal epithelial cell layers <i>in vitro</i>, allowing paracellular transport of molecules of up to 4 kDa. Protein kinase C zeta (PKC ζ), a member of a family of serine/threonine kinases was shown to be involved in tight junction modulation induced by L-R5. We show here that the ability of L-R5 to modulate tight junctions is comparable to other permeability enhancers such as bilobalide, latrunculin A or C₁₀. Interaction of the peptide with the target protein occurs via electrostatic interaction, with the presence of positive charges being essential for its functionality. L-R5 is myristoylated to allow quick cell entry and onset of activity. While no epithelial cytotoxicity was detected, the hydrophobic myristoyl rest was shown to cause haemolysis. Taken together, these data show that a structural optimization of L-R5 may be possible, both from a toxicological and an efficacy point of view.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":"11 1","pages":"2060692"},"PeriodicalIF":3.1,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1c/76/KTIB_11_2060692.PMC9870020.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10599382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial effluxome as a barrier against antimicrobial agents: structural biology aspects and drug targeting.","authors":"Pownraj Brindangnanam,&nbsp;Ajit Ramesh Sawant,&nbsp;K Prashanth,&nbsp;Mohane Selvaraj Coumar","doi":"10.1080/21688370.2021.2013695","DOIUrl":"https://doi.org/10.1080/21688370.2021.2013695","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) is fast becoming a medical crisis affecting the entire global population. The bacterial membrane is the first layer of defense for the bacteria against antimicrobial agents (AMA), specifically transporters in the membrane efflux these AMA out of the bacteria and plays a significant role in the AMR development. Understanding the structure and the functions of these efflux transporters is essential to overcome AMR. This review discusses efflux transporters (primary, secondary, and tripartite), their domain architectures, substrate specificities, and efflux pump inhibitors (EPI). Special emphasis on nosocomial ESKAPEE (<i>Enterococcus faecium., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter</i> spp. and <i>Escherichia coli</i>) pathogens, their multidrug efflux targets and inhibitors are discussed. Deep knowledge about the functioning of efflux pumps and their structural aspects will open up opportunities for developing new EPI, which could be used along with AMA as combination therapy to overcome the emerging AMR crisis.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":"10 4","pages":"2013695"},"PeriodicalIF":3.1,"publicationDate":"2022-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9621062/pdf/KTIB_10_2013695.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10423375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Destiny of airway disease: interplay between epithelial barrier and the innate immune system.","authors":"Hasan Yüksel,&nbsp;Seda Tunca","doi":"10.1080/21688370.2021.2020706","DOIUrl":"https://doi.org/10.1080/21688370.2021.2020706","url":null,"abstract":"<p><p>When the organism encounters a foreign substance, it responds with mutual and regular interactions at different stages of the immune system. In airway diseases, the first encounter is at the epithelial level, where innate immune cells and their responses form the first leg of the protective mechanism. The most important barrier for environmental damage is the epithelial barrier. However, the epithelial barrier is not just a mechanical barrier. The formation of the microbiome on the epithelium and the tolerance or intolerance to environmental factors are vital. This vital balance is maintained between the epithelial surface and the subepithelial innate immune system. This is achieved by the epithelial line, which is a mechanical and functional barrier between them. In this respect, epithelial barrier function preservation has an important role in the development and prognosis of airway disease.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":"10 4","pages":"2020706"},"PeriodicalIF":3.1,"publicationDate":"2022-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9624204/pdf/KTIB_10_2020706.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10450704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell penetrating peptides coupled to an endothelial nitric oxide synthase sequence alter endothelial permeability.","authors":"Stephen R Koch,&nbsp;Ryan J Stark","doi":"10.1080/21688370.2021.2017226","DOIUrl":"https://doi.org/10.1080/21688370.2021.2017226","url":null,"abstract":"<p><p>Delivery of cargo to cells through the use of cell-penetrating peptide (CPP) sequences is an area of rich investigation for targeted therapeutics. Specific to the endothelium, the layer of cells that cover every blood vessel in the body, the loss or alteration of a key enzyme, endothelial nitric oxide synthase (eNOS), is known to contribute to endothelial health during severe, infectious challenge. While the beneficial effects of eNOS are often thought to be mediated through the generation of nitric oxide, some protection is theorized to be through eNOS binding to regulatory pathways via a pentabasic RRKRK motif. We hypothesized that delivery of the eNOS-RRKRK peptide sequence using common CPPs would allow protection against gram-negative lipopolysaccharide (LPS). Combination of the eNOS-RRKRK sequence to the CPP antennapedia (AP) reduced the impact of LPS-induced permeability in cultured human microvascular endothelial cells (HMVECs) as measured by transendothelial electrical resistance (TEER). There was also a modest reduction in cytokine production, however it was observed that AP alone significantly impaired LPS-induced endothelial permeability and cytokine production. In comparison, the CPP trans-activator of transcription (TAT) did not significantly alter endothelial inflammation by itself. When TAT was coupled to the eNOS-RRKRK sequence, protection against LPS-induced permeability was still demonstrated, however cytokine production was not reduced. These data demonstrate that the RRKRK sequence of eNOS can offer some NO-independent protection against LPS-mediated endothelial inflammation, however the degree of protection is highly dependent on the type of CPP utilized for cargo delivery.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":"10 4","pages":"2017226"},"PeriodicalIF":3.1,"publicationDate":"2022-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9621006/pdf/KTIB_10_2017226.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10439074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}