Retinoid Regulation of Ocular Surface Innate Inflammation
Abstract
:1. Introduction
2. Results and Discussion
2.1. Lacrimal Glands Secrete Vitamin A into Tears that Is Metabolized on the Ocular Surface
2.2. Retinoic Acid Receptor Expression on the Ocular Surface
2.3. Effects of Retinoic Acid on Innate Immune Cells
3. Conclusions
4. Materials and Methods
4.1. Animals and Vitamin A Deficiency Protocol
4.2. Measurement of Goblet Cell Density
4.3. Immunofluorescent Staining
4.4. Real-Time PCR
4.5. Western Blot
4.6. Flow Cytometry
4.7. Measurement of NFκB p65 Activation
4.8. RNA Seq Data Analysis
4.9. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Semba, R.D. The discovery of the vitamins. Int. J. Vitam. Nutr. Res. 2012, 82, 310–315. [Google Scholar] [PubMed]
- Wolf, G. The discovery of the visual function of vitamin A. J. Nutr. 2001, 131, 1647–1650. [Google Scholar] [PubMed]
- Reboul, E. Absorption of vitamin A and carotenoids by the enterocyte: Focus on transport proteins. Nutrients 2013, 5, 3563–3581. [Google Scholar]
- Von Lintig, J.; Babino, D. Chapter 31—Vitamin A and Other Carotenoids. In Principles of Nutrigenetics and Nutrigenomics; Caterina, R.D.E., Martinez, J.A., Kohlmeier, M., Eds.; Academic Press: Cambridge, MA, USA, 2020; pp. 237–244. [Google Scholar]
- O’Byrne, S.M.; Blaner, W.S. Retinol and retinyl esters: Biochemistry and physiology. J. Lipid Res. 2013, 54, 1731–1743. [Google Scholar] [PubMed] [Green Version]
- Harrison, E.H. Mechanisms of digestion and absorption of dietary vitamin A. Annu. Rev. Nutr. 2005, 25, 87–103. [Google Scholar] [PubMed]
- Sun, H.; Kawaguchi, R. The membrane receptor for plasma retinol-binding protein, a new type of cell-surface receptor. Int. Rev. Cell. Mol. Biol. 2011, 288, 1–41. [Google Scholar] [PubMed] [Green Version]
- Ubels, J.L.; Osgood, T.B.; Foley, K.M. Vitamin A is stored as fatty acyl esters of retinol in the lacrimal gland. Curr. Eye Res. 1988, 7, 1009–1016. [Google Scholar]
- Ubels, J.L.; Rismondo, V.; Osgood, T.B. The relationship between secretion of retinol and protein by the lacrimal gland. Investig. Ophthalmol. Vis. Sci. 1989, 30, 952–960. [Google Scholar]
- Ubels, J.L.; Foley, K.M.; Rismondo, V. Retinol secretion by the lacrimal gland. Investig. Ophthalmol. Vis. Sci. 1986, 27, 1261–1268. [Google Scholar]
- Hayashi, K.; Reddy, C.; Hanninen, L.; Wolf, G.; Kenyon, K.R. Pathologic changes in the exorbital lacrimal gland of the vitamin A-deficient rat. Investig. Ophthalmol. Vis. Sci. 1990, 31, 187–196. [Google Scholar]
- Zabetian-Targhi, F.; Mahmoudi, M.J.; Rezaei, N.; Mahmoudi, M. Retinol binding protein 4 in relation to diet, inflammation, immunity, and cardiovascular diseases. Adv. Nutr. 2015, 6, 748–762. [Google Scholar] [PubMed] [Green Version]
- Xiao, Y.; De Paiva, C.S.; Yu, Z.; Guimaraes de Souza, R.; Li, D.Q.; Pflugfelder, S.C. Goblet cell produced retinoic acid suppresses CD86 expression and IL-12 production in bone marrow derived cells. Int. Immunol. 2018, 25, 457–470. [Google Scholar]
- Coursey, T.G.; Tukler Henriksson, J.; Barbosa, F.L.; de Paiva, C.S.; Pflugfelder, S.C. Interferon-gamma-Induced Unfolded Protein Response in Conjunctival Goblet Cells as a Cause of Mucin Deficiency in Sjogren Syndrome. Am. J. Pathol. 2016, 186, 1547–1558. [Google Scholar]
- Bian, F.; Xiao, Y.; Barbosa, F.L.; de Souza, R.G.; Hernandez, H.; Yu, Z.; Pflugfelder, S.C.; de Paiva, C.S. Age-associated antigen-presenting cell alterations promote dry-eye inducing Th1 cells. Mucosal Immunol. 2019, 12, 897–908. [Google Scholar]
- Pflugfelder, S.C.; Bian, F.; Gumus, K.; Farley, W.; Stern, M.E.; De Paiva, C.S. Severity of Sjogren’s Syndrome Keratoconjunctivitis Sicca Increases with Increased Percentage of Conjunctival Antigen-Presenting Cells. Int. J. Mol. Sci. 2018, 19, 2760. [Google Scholar]
- Mori, M.; Ghyselinck, N.B.; Chambon, P.; Mark, M. Systematic immunolocalization of retinoid receptors in developing and adult mouse eyes. Investig. Ophthalmol. Vis. Sci. 2001, 42, 1312–1318. [Google Scholar]
- Suzuki, T.; Richards, S.M.; Liu, S.; Jensen, R.V.; Sullivan, D.A. Influence of sex on gene expression in human corneal epithelial cells. Mol. Vis. 2009, 15, 2554–2569. [Google Scholar] [PubMed]
- Alam, J.; de Paiva, C.S.; Pflugfelder, S.C. Immune—Goblet cell interaction in the conjunctiva. Ocul. Surf. 2020, 18, 326–334. [Google Scholar]
- Corrales, R.M.; Villarreal, A.; Farley, W.; Stern, M.E.; Li, D.Q.; Pflugfelder, S.C. Strain-related cytokine profiles on the murine ocular surface in response to desiccating stress. Cornea 2007, 26, 579–584. [Google Scholar]
- Ko, B.Y.; Xiao, Y.; Barbosa, F.L.; de Paiva, C.S.; Pflugfelder, S.C. Goblet cell loss abrogates ocular surface immune tolerance. JCI Insight 2018, 3, e98222. [Google Scholar]
- Du, X.; Tabeta, K.; Mann, N.; Crozat, K.; Mudd, S.; Beutler, B. An essential role for Rxr alpha in the development of Th2 responses. Eur. J. Immunol. 2005, 35, 3414–3423. [Google Scholar] [CrossRef] [PubMed]
- Alam, J.; de Souza, R.G.; Yu, Z.; Stern, M.E.; de Paiva, C.S.; Pflugfelder, S.C. Calcineurin Inhibitor Voclosporin Preserves Corneal Barrier and Conjunctival Goblet Cells in Experimental Dry Eye. J. Ocul. Pharmacol. Ther. Off. J. Assoc. Ocul. Pharmacol. Ther. 2020, 36, 679–685. [Google Scholar] [CrossRef] [PubMed]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Alam, J.; Yu, Z.; de Paiva, C.S.; Pflugfelder, S.C. Retinoid Regulation of Ocular Surface Innate Inflammation. Int. J. Mol. Sci. 2021, 22, 1092. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031092
Alam J, Yu Z, de Paiva CS, Pflugfelder SC. Retinoid Regulation of Ocular Surface Innate Inflammation. International Journal of Molecular Sciences. 2021; 22(3):1092. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031092
Chicago/Turabian StyleAlam, Jehan, Zhiyuan Yu, Cintia S. de Paiva, and Stephen C. Pflugfelder. 2021. "Retinoid Regulation of Ocular Surface Innate Inflammation" International Journal of Molecular Sciences 22, no. 3: 1092. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031092