title: Amniotic membrane modulates innate immune response inhibiting PRRs expression and NF-κB nuclear translocation on limbal myofibroblasts.
abstract: Corneal damage observed in a viral infection such as herpetic stromal keratitis is mainly caused by proinflammatory molecules released by resident cells in the response to viral antigens. There are pattern recognition receptors like MDA5, RIG-1, and TLR3, that recognize viral dsRNA and after activation, the innate immune response is exacerbated inducing the synthesis and secretion of inflammatory cytokines through NF-κB activation. Amniotic membrane (AM) has demonstrated to reduce inflammation by several mechanisms, however the effect of AM on innate immune receptors such as MDA5, RIG-1, and TLR3 has not been reported. In this study, we have determined that the presence of AM significantly inhibited the synthesis and secretion of proinflammatory cytokines on human limbal myofibroblasts (HLM) stimulated with poly I:C. Similarly, the presence of AM reduced the protein expression of MDA5, RIG-1, and TLR3 on poly I:C stimulated HLM. Additionally, the presence of the AM significantly inhibited the NF-κB nuclear translocation when the HLM were poly I:C stimulated, and concomitantly, the AM was able to relocate cadherins affecting the myofibroblastic cellular morphology. These results suggest that AM generates an anti-inflammatory microenvironment, and specific inhibition of NFκB nuclear translocation on infected corneal tissue would reduce the inflammation undesirable effects, explaining in part the beneficial usefulness of transplanting AM on herpetic stromal keratitis.
authors.affiliation: Research Unit, Institute of Ophthalmology Conde de Valenciana Foundation, Chimalpopoca 14, 06800 Mexico City, Mexico; Department of Biochemistry, Faculty of Medicine, Universidad Nacional Autónoma de México, Insurgentes Sur 3000, 04510 Mexico City, Mexico.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Domínguez-López
authors.affiliation: Research Unit, Institute of Ophthalmology Conde de Valenciana Foundation, Chimalpopoca 14, 06800 Mexico City, Mexico.
authors.forename: Victor Manuel
authors.initials: VM
authors.lastname: Bautista-de Lucio
authors.affiliation: Department of Immunology, National School of Biological Sciences, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala, 11340 Mexico City, Mexico.
authors.forename: Janet
authors.initials: J
authors.lastname: Serafín-López
authors.affiliation: Research Unit, Institute of Ophthalmology Conde de Valenciana Foundation, Chimalpopoca 14, 06800 Mexico City, Mexico; Department of Biochemistry, Faculty of Medicine, Universidad Nacional Autónoma de México, Insurgentes Sur 3000, 04510 Mexico City, Mexico.
authors.forename: Edson
authors.initials: E
authors.lastname: Robles-Sánchez
authors.affiliation: Research Unit, Institute of Ophthalmology Conde de Valenciana Foundation, Chimalpopoca 14, 06800 Mexico City, Mexico; Department of Biochemistry, Faculty of Medicine, Universidad Nacional Autónoma de México, Insurgentes Sur 3000, 04510 Mexico City, Mexico. Electronic address: yogarfias@yahoo.com.
authors.forename: Yonathan
authors.initials: Y
authors.lastname: Garfias
mesh_terms: D000650:Amnion / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D016850:Limbus Corneae / Q000166:cytology*; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D021381:Protein Transport; D051192:Receptors, Pattern Recognition / Q000378:metabolism*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D051192:Receptors, Pattern Recognition; D011070:Poly I-C
keywords: MDA-5; RIG-1; TLR-3; amniotic membrane; inflammatory cytokines; limbal myofibroblasts