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The Pro-inflammatory Cytokine Interleukin-6 Regulates Nanoparticle Transport Across Model Follicle-Associated Epithelium Cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Otsuka Pharmaceut Co Ltd, Formulat Res Inst, BA Project, 224-18 Ebino, Kawaguchi, Tokushima 7710182, Japan..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2016 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 105, no 7, 2099-2104 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate whether the pro-inflammatory cytokines improved the function of the cell monolayer model of the human follicle-associated epithelium (FAE) of co-culture of Caco-2 cells on permeable filters with Raji B-cells underneath from the viewpoint of particle transport. Exposure to tumor necrosis factor-a resulted in an almost maintained epithelial integrity/paracellular permeability combined with an increased nanoparticle transport in a dose-dependent manner while the effects of interleukin (IL)-1 beta were limited. Exposure to IL-6 significantly enhanced the nanoparticle transport with the limited disruption of the cell monolayer integrity. The addition of IL-6 or tumor necrosis factor-a to Caco-2 monolayers without Raji B-cells did not enhance nanoparticle transport. In our IL-6 treated FAE model, the nanoparticle transport almost disappeared at 4 degrees C or after the addition of 5-(N-ethyl-N-isopropyl) amiloride, an inhibitor of macropinocytosis. Furthermore, IgA binding, presumably by a secretory IgA receptor, a marker of M-cells was observed on the apical side of our model FAE. These results indicate that the combined effect of IL-6 with unknown factors from Raji-B cells made the FAE model more functional with regard to nanoparticle transport. The IL-6 enhanced FAE model will be a useful platform for nanoparticle drug delivery research across the intestinal epithelium.

Place, publisher, year, edition, pages
2016. Vol. 105, no 7, 2099-2104 p.
Keyword [en]
M-cells, pro-inflammatory cytokine, IL-6, nanoparticle, absorption improving, sIgA receptor
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-303132DOI: 10.1016/j.xphs.2016.03.043ISI: 000381770300009PubMedID: 27262206OAI: oai:DiVA.org:uu-303132DiVA: diva2:971164
Available from: 2016-09-15 Created: 2016-09-15 Last updated: 2016-09-15Bibliographically approved

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