The extracellular matrix (ECM) plays a crucial role in organoid cultures by supporting cell proliferation and differentiation. A key feature of the ECM is its mechanical influence on the surrounding cells, directly affecting their behavior. Matrigel, the most commonly used ECM, is limited by its animal-derived origin, batch variability, and uncontrollable mechanical properties, restricting its use in 3D cell-model-based mechanobiological studies. Poly(2-alkyl-2-oxazoline) (PAOx) synthetic hydrogels represent an appealing alternative because of their reproducibility and versatile chemistry, enabling tuning of hydrogel stiffness and functionalization. Here, we studied PAOx hydrogels with differing compressive moduli for their potential to support 3D cell growth. PAOx hydrogels support spheroid and organoid growth over several days without the addition of ECM components. Furthermore, we discovered intestinal organoid epithelial polarity reversion in PAOx hydrogels and demonstrate how the tunable mechanical properties of PAOx can be used to study effects on the morphology and oxygenation of live multicellular spheroids.
- Publikační typ
- časopisecké články MeSH
Natural compounds offer a wide spectrum of potential active substances, but often they have a poor bioavailability. To increase the bioavailability and bioactivity of the natural anti-inflammatory molecules curcumin and diplacone, we used glucan particles (GPs), hollow shells from Saccharomyces cerevisiae composed mainly of β-1,3-d-glucan. Their indigestibility and relative stability in the gut combined with their immunomodulatory effects makes them promising carriers for such compounds. This study aimed to determine how curcumin and diplacone, either alone or incorporated in GPs, affect the immunomodulatory activity of the latter by assessing the respiratory burst response and the secretion of pro-inflammatory cytokines by primary porcine innate immune cells. Incorporating curcumin and diplacone into GPs by controlled evaporation of the organic solvent substantially reduced the respiratory burst response mediated by GPs. Incorporated curcumin in GPs also reduced GPs mediated secretion of IL-1β and TNF-α by innate immune cells. The obtained results indicate a potentially beneficial effect of the incorporation of curcumin or diplacone into GPs against inflammation.
- Klíčová slova
- Blood immune cells, Curcumin, Diplacone, Glucan particles, Immunomodulatory effect, Inflammation,
- MeSH
- antiflogistika chemie farmakologie MeSH
- beta-glukany chemie izolace a purifikace farmakologie MeSH
- flavanony chemie farmakologie MeSH
- imunologické faktory chemie izolace a purifikace farmakologie MeSH
- interleukin-1beta metabolismus MeSH
- kultivované buňky MeSH
- kurkumin chemie farmakologie MeSH
- leukocyty mononukleární účinky léků imunologie metabolismus MeSH
- neutrofily účinky léků imunologie metabolismus MeSH
- nosiče léků * MeSH
- příprava léků MeSH
- proteoglykany MeSH
- respirační vzplanutí účinky léků MeSH
- rozpouštědla chemie MeSH
- Saccharomyces cerevisiae chemie MeSH
- Sus scrofa MeSH
- TNF-alfa metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiflogistika MeSH
- beta-glukany MeSH
- diplacone MeSH Prohlížeč
- flavanony MeSH
- imunologické faktory MeSH
- interleukin-1beta MeSH
- kurkumin MeSH
- nosiče léků * MeSH
- polysaccharide-K MeSH Prohlížeč
- proteoglykany MeSH
- rozpouštědla MeSH
- TNF-alfa MeSH
BACKGROUND: Helicobacter (H.) suis is mainly associated with pigs, but is also the most prevalent gastric non-H. pylori Helicobacter species found in humans. Both H. pylori and H. suis may cause persistent infection of the stomach. Several immune evasion mechanisms have been proposed for H. pylori, which focus to a great extent on its major virulence factors, which are absent in H. suis. The aim of this study was to gain more knowledge on immune evasion by H. suis. MATERIALS AND METHODS: Cytokine expression kinetics were monitored in the stomach of BALB/c mice experimentally infected with H. suis. The cytokine expression profile in the stomach of naturally H. suis-infected pigs was also determined. Subsequently, the effect of H. suis on murine and porcine dendritic cell (DC) maturation and their ability to elicit T-cell effector responses was analyzed. RESULTS: Despite a Th17/Th2 response in the murine stomach, the inflammatory cell influx was unable to clear H. suis infection. H. suis-stimulated murine bone marrow-derived dendritic cells induced IL-17 secretion by CD4+ cells in vitro. Natural H. suis infection in pigs evoked increased expression levels of IL-17 mRNA in the antrum and IL-10 mRNA in the fundus. In contrast to mice, H. suis-stimulated porcine monocyte-derived dendritic cells were unable to express MHCII molecules on their cell surface. These semimature DCs induced proliferation of T-cells, which showed an increased expression of TGF-β and FoxP3 mRNA levels. CONCLUSIONS: Helicobacter suis might evade host immune responses by skewing toward a Treg-biased response.
- Klíčová slova
- Helicobacter suis, BALB/c mice, Pig, immune response,
- MeSH
- cytokiny metabolismus MeSH
- Helicobacter heilmannii imunologie MeSH
- imunitní únik * MeSH
- infekce vyvolané Helicobacter pylori imunologie mikrobiologie veterinární MeSH
- interakce hostitele a patogenu * MeSH
- myši inbrední BALB C MeSH
- prasata MeSH
- stanovení celkové genové exprese MeSH
- T-lymfocyty imunologie MeSH
- žaludek imunologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cytokiny MeSH