Citation: Vicente-Fermín, O.; Zenteno, E.; Ramos-Martínez, I.; Espitia, C.; Sánchez-Betancourt, J.I.; Huerta, L. Effect of Dexamethasone on the Expression of the α2,3 and α2,6 Sialic Acids in Epithelial Cell Lines. Pathogens 2022, 11, 1518. https://doi.org/10.3390/ pathogens11121518 Academic Editors: Jesús Hernández, Janice Reis Ciacci-Zanella and Lawrence S. Young Received: 19 October 2022 Accepted: 25 November 2022 Published: 12 December 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 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 (https:// creativecommons.org/licenses/by/ 4.0/). pathogens Article Effect of Dexamethasone on the Expression of the α2,3 and α2,6 Sialic Acids in Epithelial Cell Lines Onasis Vicente-Fermín 1 , Edgar Zenteno 2 , Ivan Ramos-Martínez 3 , Clara Espitia 1 , José Ivan Sánchez-Betancourt 3 and Leonor Huerta 1, * 1 Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México 04510, Mexico 2 Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México 04510, Mexico 3 Departamento de Medicina y Zootecnia de Cerdos, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México 04510, Mexico * Correspondence: leonorhh@iibiomedicas.unam.mx; Tel.: +52-(55)-56-22-38-83 Abstract: N-acetylneuraminic acid linked to galactose by α2,6 and α2,3 linkages (Siaα2,6 and Siaα2,3) is expressed on glycoconjugates of animal tissues, where it performs multiple biological functions. In addition, these types of sialic acid residues are the main targets for the binding and entry of influenza viruses. Here we used fluorochrome-conjugated Sambuccus nigra, Maackia amurensis, and peanut lectins for the simultaneous detection of Siaα2,3 and Siaα2,6 and galactosyl residues by two-color flow cytometry on A549 cells, a human pneumocyte cell line used for in vitro studies of the infection by influenza viruses, as well as on Vero and MDCK cell lines. The dexamethasone (DEX) glucocorticoid (GC), a widely used anti-inflammatory compound, completely abrogated the expression of Siaα2,3 in A549 cells and decreased its expression in Vero and MDCK cells; in contrast, the expression of Siaα2,6 was increased in the three cell lines. These observations indicate that DEX can be used for the study of the mechanism of sialylation of cell membrane molecules. Importantly, DEX may change the tropism of avian and human/pig influenza viruses and other infectious agents to animal and human epithelial cells. Keywords: sialic acid; A549; MDCK; Vero; dexamethasone; influenza receptors; zoonosis; sialylation 1. Introduction Terminal N-acetylneuraminic acid (Neu5Ac, Sia) linked to β-galactose by α2,3 or α2,6 linkages (Siaα2,3 and Siaα2,6, respectively) and mucin-type O-glycans containing Gal and GalNAc (Gal-β(1-3)-GalNAc, Thomsen–Friedenreich antigen) are present on glycoproteins and glycolipids on cell membranes and are involved in cell–cell interaction [1], signaling processes [2], cell–substrate interactions, and differentiation [3–5]. Particularly, aberrant expression of terminal α2,6 Neu5Ac and Gal-β(1-3)-GalNAc is found in a variety of tumors [6–9] The biological relevance of Siaα2,3 and Siaα2,6 is increased by the fact that they are the main receptors for influenza viruses that infect epithelial cells from several animal species and humans [10,11]. Dexamethasone (DEX) is a potent synthetic glucocorticoid derived from hydrocorti- sone, and so it regulates carbohydrate and protein metabolism. Pharmacologically, DEX has anti-inflammatory, anti-allergic, and immunosuppressive effects, so it is widely used in the treatment of respiratory distress and other inflammatory conditions both in humans and farm animals. Mechanisms of action of DEX are highly diverse and are mediated by binding to both cytoplasmic and membrane receptors, forming complexes (GC-GCR) which directly suppress the expression of genes encoding for pro-inflammatory proteins, inactivate transcription factors, and induce modification of gene expression by epigenetic mechanisms. Other effects described are the skewing of the cell metabolism by reduction Pathogens 2022, 11, 1518. https://doi.org/10.3390/pathogens11121518 https://www.mdpi.com/journal/pathogens