دورية أكاديمية
The Fusion Protein rFlaA:Betv1 Modulates DC Responses by a p38-MAPK and COX2-Dependent Secretion of PGE2 from Epithelial Cells
| العنوان: | The Fusion Protein rFlaA:Betv1 Modulates DC Responses by a p38-MAPK and COX2-Dependent Secretion of PGE2 from Epithelial Cells |
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| المؤلفون: | Yen-Ju Lin, Adam Flaczyk, Sonja Wolfheimer, Alexandra Goretzki, Annette Jamin, Andrea Wangorsch, Stefan Vieths, Stephan Scheurer, Stefan Schülke |
| المصدر: | Cells, Vol 10, Iss 12, p 3415 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Cytology |
| مصطلحات موضوعية: | flagellin, Betv1, epithelial cells, vaccine, fusion protein, Cytology, QH573-671 |
| الوصف: | Developing new adjuvants/vaccines and better understanding their mode-of-action is an important task. To specifically improve birch pollen allergy treatment, we designed a fusion protein consisting of major birch pollen allergen Betv1 conjugated to the TLR5-ligand flagellin (rFlaA:Betv1). This study investigates the immune-modulatory effects of rFlaA:Betv1 on airway epithelial cells. LA-4 mouse lung epithelial cells were stimulated with rFlaA:Betv1 in the presence/absence of various inhibitors with cytokine- and chemokine secretion quantified by ELISA and activation of intracellular signaling cascades demonstrated by Western blot (WB). Either LA-4 cells or LA-4-derived supernatants were co-cultured with BALB/c bone marrow-derived myeloid dendritic cells (mDCs). Compared to equimolar amounts of flagellin and Betv1 provided as a mixture, rFlaA:Betv1 induced higher secretion of IL-6 and the chemokines CCL2 and CCL20 from LA-4 cells and a pronounced MAPK- and NFκB-activation. Mechanistically, rFlaA:Betv1 was taken up more strongly and the induced cytokine production was inhibited by NFκB-inhibitors, while ERK- and p38-MAPK-inhibitors only suppressed IL-6 and CCL2 secretion. In co-cultures of LA-4 cells with mDCs, rFlaA:Betv1-stimulated LA-4 cells p38-MAPK- and COX2-dependently secreted PGE2, which modulated DC responses by suppressing pro-inflammatory IL-12 and TNF-α secretion. Taken together, these results contribute to our understanding of the mechanisms underlying the strong immune-modulatory effects of flagellin-containing fusion proteins. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 10123415 2073-4409 |
| العلاقة: | https://www.mdpi.com/2073-4409/10/12/3415Test; https://doaj.org/toc/2073-4409Test |
| DOI: | 10.3390/cells10123415 |
| الوصول الحر: | https://doaj.org/article/ada92b2bd4b242b78ca3ffc836ea0bb8Test |
| رقم الانضمام: | edsdoj.92b2bd4b242b78ca3ffc836ea0bb8 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 10123415 20734409 |
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| DOI: | 10.3390/cells10123415 |