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1.
PLoS One ; 16(11): e0260181, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34788346

RESUMEN

Due to its increasing production, durability and multiple applications, plastic is a material we encounter every day. Small plastic particles from the µm to the mm range are classified as microplastics and produced for cosmetic and medical products, but are also a result of natural erosion and decomposition of macroplastics. Although being omnipresent in our environment and already detected in various organisms, less is known about the effects of microplastics on humans in general, or on vascular biology in particular. Here we investigated the effects of carboxylated polystyrene microplastic particles (PS, 1 µm) on murine endothelial and immune cells, which are both crucially involved in vascular inflammation, using in vitro and in vivo approaches. In vitro, PS induced adhesion molecule expression in endothelial cells with subsequent adhesion of leukocytes both under static and flow conditions. In monocytic cells, PS enhanced pro-inflammatory cytokine expression and release. Accordingly, administering mice with PS led to enhanced aortic expression of cytokines and adhesion molecules. Furthermore, we identified neutrophils as the PS-clearing blood leukocyte population. The findings from this study for the first time indicate polystyrene microplastic as a new environmental risk factor for endothelial inflammation.


Asunto(s)
Células Endoteliales/efectos de los fármacos , Microplásticos/efectos adversos , Plásticos/efectos adversos , Poliestirenos/efectos adversos , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Ácidos Carboxílicos/efectos adversos , Línea Celular , Citocinas/metabolismo , Células Endoteliales/metabolismo , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo
2.
Gut Microbes ; 12(1): 1-17, 2020 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-33079623

RESUMEN

Although it is generally accepted that dietary fiber is health promoting, the underlying immunological and molecular mechanisms are not well defined, especially with respect to cellulose, the most ubiquitous dietary fiber. Here, the impact of dietary cellulose on intestinal microbiota, immune responses and gene expression in health and disease was examined. Lack of dietary cellulose disrupted the age-related diversification of the intestinal microbiota, which subsequently remained in an immature state. Interestingly, one of the most affected microbial genera was Alistipes which is equipped with enzymes to degrade cellulose. Absence of cellulose changed the microbial metabolome, skewed intestinal immune responses toward inflammation, altered the gene expression of intestinal epithelial cells and mice showed increased sensitivity to colitis induction. In contrast, mice with a defined microbiota including A. finegoldii showed enhanced colonic expression of intestinal IL-22 and Reg3γ restoring intestinal barrier function. This study supports the epidemiological observations and adds a causal explanation for the health promoting effects of the most common biopolymer on earth.


Asunto(s)
Celulosa/metabolismo , Fibras de la Dieta/metabolismo , Células Epiteliales/metabolismo , Microbioma Gastrointestinal/fisiología , Mucosa Intestinal/inmunología , Animales , Antiinflamatorios/metabolismo , Bacteroidetes/metabolismo , Colitis/patología , Inflamación/patología , Interleucinas/biosíntesis , Mucosa Intestinal/microbiología , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Asociadas a Pancreatitis/biosíntesis , Interleucina-22
3.
J Biol Chem ; 277(12): 10683-90, 2002 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-11773049

RESUMEN

The apical sorting of human intestinal dipeptidyl peptidase IV (DPPIV) occurs through complex N-linked and O-linked carbohydrates. Inhibition of O-linked glycosylation by benzyl-N-acetyl-alpha-d-galactosaminide affects significantly the sorting behavior of DPPIV in intestinal Caco-2 and HT-29 cells. However, random delivery to the apical and basolateral membranes and hence a more drastic effect on the sorting of DPPIV in both cell types is only observed when, in addition to O-glycans, the processing of N-glycans is affected by swainsonine, an inhibitor of mannosidase II. Together the data indicate that both types of glycosylation are critical components of the apical sorting signal of DPPIV. The sorting mechanism of DPPIV implicates its association with detergent-insoluble membrane microdomains containing cholesterol and sphingolipids, whereas an efficient association largely depends on the presence of a fully complex N- and O-linked glycosylated DPPIV. Interestingly, cholesterol is a more critical component in this context than sphingolipids, because cholesterol depletion by beta-cyclodextrin affects the detergent solubility and the sorting behavior of DPPIV more strongly than fumonisin, an inhibitor of sphingolipid synthesis.


Asunto(s)
Acetilgalactosamina/análogos & derivados , Dipeptidil Peptidasa 4/química , Dipeptidil Peptidasa 4/metabolismo , Intestinos/enzimología , Microdominios de Membrana/metabolismo , Polisacáridos/química , Acetilgalactosamina/farmacología , Compuestos de Bencilo/farmacología , Células CACO-2 , Línea Celular , Membrana Celular/metabolismo , Colesterol/metabolismo , Ciclodextrinas/metabolismo , Detergentes/farmacología , Electroforesis en Gel de Poliacrilamida , Inhibidores Enzimáticos/farmacología , Glicósido Hidrolasas/metabolismo , Glicosilación , Humanos , Manosidasas/farmacología , Microdominios de Membrana/química , Octoxinol/farmacología , Unión Proteica , Estructura Terciaria de Proteína , Serina Endopeptidasas/metabolismo , Swainsonina/farmacología , Tripsina/farmacología
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