Potentiation of IL-4 Signaling by Retinoic Acid in Intestinal Epithelial Cells and Macrophages—Mechanisms and Targets
We previously demonstrated that IL4, IL13, CLCA1, and CCL26 mRNA were significantly upregulated in the lungs of pigs given a low dose of all trans-retinoic acid (ATRA) and infected with Ascaris suum. We also demonstrated that in vitro ATRA induced a state of partial alternative activation in porcine...
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| Format: | Article |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00605/full |
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| author | Celine Chen Allen D. Smith Lumei Cheung Quynhchi Pham Joseph F. Urban Harry D. Dawson |
| author_facet | Celine Chen Allen D. Smith Lumei Cheung Quynhchi Pham Joseph F. Urban Harry D. Dawson |
| author_sort | Celine Chen |
| collection | DOAJ |
| description | We previously demonstrated that IL4, IL13, CLCA1, and CCL26 mRNA were significantly upregulated in the lungs of pigs given a low dose of all trans-retinoic acid (ATRA) and infected with Ascaris suum. We also demonstrated that in vitro ATRA induced a state of partial alternative activation in porcine macrophages (Mφs) and amplified certain aspects of M2a activation induced by IL-4. Given these results, we tested the effect of ATRA on IL-4 responses in two porcine intestinal epithelial cell lines, IPEC1 and IPEC-J2 and observed that ATRA increased mRNA for the IL-4 receptor alpha chain. ATRA also increased IL-4 induced phosphorylation of signal transducer and activator of transcription 6 (STAT6) and mRNA expression of the chloride channel, calcium activated, family member 1 (CLCA1), important for mucus formation, and chemokine (C-C motif) ligand 26 (CCL26), a potent eosinophil chemoattractant. We extended these findings to human Mφ THP-1 cells and showed that ATRA synergistically increased IL-4–induced CCL2, CCL13, and CCL26 mRNA and protein levels. Transglutaminase 2 mRNA, protein, and enzyme activity were synergistically induced in THP-1 cells pretreated with ATRA and then treated with IL-4, thus, ATRA increased signaling in response to IL-4 in porcine epithelial cells and porcine and human Mφs. Given the prevalence of allergic and parasitic diseases worldwide and the close similarities in the porcine and human immune responses, these findings have important implications for the nutritional regulation of allergic inflammation at mucosal surfaces. |
| first_indexed | 2024-12-11T14:39:00Z |
| format | Article |
| id | doaj.art-cdf57127dc5c484b8f7f72208a4eb279 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T14:39:00Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-cdf57127dc5c484b8f7f72208a4eb2792022-12-22T01:02:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00605500300Potentiation of IL-4 Signaling by Retinoic Acid in Intestinal Epithelial Cells and Macrophages—Mechanisms and TargetsCeline ChenAllen D. SmithLumei CheungQuynhchi PhamJoseph F. UrbanHarry D. DawsonWe previously demonstrated that IL4, IL13, CLCA1, and CCL26 mRNA were significantly upregulated in the lungs of pigs given a low dose of all trans-retinoic acid (ATRA) and infected with Ascaris suum. We also demonstrated that in vitro ATRA induced a state of partial alternative activation in porcine macrophages (Mφs) and amplified certain aspects of M2a activation induced by IL-4. Given these results, we tested the effect of ATRA on IL-4 responses in two porcine intestinal epithelial cell lines, IPEC1 and IPEC-J2 and observed that ATRA increased mRNA for the IL-4 receptor alpha chain. ATRA also increased IL-4 induced phosphorylation of signal transducer and activator of transcription 6 (STAT6) and mRNA expression of the chloride channel, calcium activated, family member 1 (CLCA1), important for mucus formation, and chemokine (C-C motif) ligand 26 (CCL26), a potent eosinophil chemoattractant. We extended these findings to human Mφ THP-1 cells and showed that ATRA synergistically increased IL-4–induced CCL2, CCL13, and CCL26 mRNA and protein levels. Transglutaminase 2 mRNA, protein, and enzyme activity were synergistically induced in THP-1 cells pretreated with ATRA and then treated with IL-4, thus, ATRA increased signaling in response to IL-4 in porcine epithelial cells and porcine and human Mφs. Given the prevalence of allergic and parasitic diseases worldwide and the close similarities in the porcine and human immune responses, these findings have important implications for the nutritional regulation of allergic inflammation at mucosal surfaces.https://www.frontiersin.org/article/10.3389/fimmu.2020.00605/fullmacrophageporcinehumaninterleukin 4all-trans-retinoic acid |
| spellingShingle | Celine Chen Allen D. Smith Lumei Cheung Quynhchi Pham Joseph F. Urban Harry D. Dawson Potentiation of IL-4 Signaling by Retinoic Acid in Intestinal Epithelial Cells and Macrophages—Mechanisms and Targets Frontiers in Immunology macrophage porcine human interleukin 4 all-trans-retinoic acid |
| title | Potentiation of IL-4 Signaling by Retinoic Acid in Intestinal Epithelial Cells and Macrophages—Mechanisms and Targets |
| title_full | Potentiation of IL-4 Signaling by Retinoic Acid in Intestinal Epithelial Cells and Macrophages—Mechanisms and Targets |
| title_fullStr | Potentiation of IL-4 Signaling by Retinoic Acid in Intestinal Epithelial Cells and Macrophages—Mechanisms and Targets |
| title_full_unstemmed | Potentiation of IL-4 Signaling by Retinoic Acid in Intestinal Epithelial Cells and Macrophages—Mechanisms and Targets |
| title_short | Potentiation of IL-4 Signaling by Retinoic Acid in Intestinal Epithelial Cells and Macrophages—Mechanisms and Targets |
| title_sort | potentiation of il 4 signaling by retinoic acid in intestinal epithelial cells and macrophages mechanisms and targets |
| topic | macrophage porcine human interleukin 4 all-trans-retinoic acid |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00605/full |
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