title: Interaction of IFN-γ with cholinergic agonists to modulate rat and human goblet cell function.
abstract: Goblet cells populate wet-surfaced mucosa including the conjunctiva of the eye, intestine, and nose, among others. These cells function as part of the innate immune system by secreting high molecular weight mucins that interact with environmental constituents including pathogens, allergens, and particulate pollutants. Herein, we determined whether interferon gamma (IFN-γ), a Th1 cytokine increased in dry eye, alters goblet cell function. Goblet cells from rat and human conjunctiva were cultured. Changes in intracellular [Ca(2+)] ([Ca(2+)](i)), high molecular weight glycoconjugate secretion, and proliferation were measured after stimulation with IFN-γ with or without the cholinergic agonist carbachol. IFN-γ itself increased [Ca(2+)](i) in rat and human goblet cells and prevented the increase in [Ca(2+)](i) caused by carbachol. Carbachol prevented IFN-γ-mediated increase in [Ca(2+)](i). This cross-talk between IFN-γ and muscarinic receptors may be partially due to use of the same Ca(2+)(i) reservoirs, but also from interaction of signaling pathways proximal to the increase in [Ca(2+)](i). IFN-γ blocked carbachol-induced high molecular weight glycoconjugate secretion and reduced goblet cell proliferation. We conclude that increased levels of IFN-γ in dry eye disease could explain the lack of goblet cells and mucin deficiency typically found in this pathology. IFN-γ could also function similarly in respiratory and gastrointestinal tracts.
authors.affiliation: Ocular Surface Group, Institute for Applied Ophthalmobiology (IOBA), University of Valladolid, Valladolid, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: García-Posadas
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.|Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Hodges
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.|Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.|Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Shatos
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: T
authors.initials: T
authors.lastname: Storr-Paulsen
authors.affiliation: Ocular Surface Group, Institute for Applied Ophthalmobiology (IOBA), University of Valladolid, Valladolid, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Diebold
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.|Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Dartt
mesh_terms: D000818:Animals; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D020013:Calcium Signaling; D002217:Carbachol / Q000494:pharmacology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D018679:Cholinergic Agonists / Q000494:pharmacology*; D003228:Conjunctiva / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D004347:Drug Interactions; D015352:Dry Eye Syndromes / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D024602:Glyceraldehyde-3-Phosphate Dehydrogenase (NADP+)(Phosphorylating) / Q000235:genetics / Q000276:immunology; D006001:Glycoconjugates / Q000096:biosynthesis / Q000378:metabolism; D020397:Goblet Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D055271:Mucin 5AC / Q000235:genetics / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018679:Cholinergic Agonists; D006001:Glycoconjugates; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D007371:Interferon-gamma; D002217:Carbachol; D024602:Glyceraldehyde-3-Phosphate Dehydrogenase (NADP+)(Phosphorylating); D002118:Calcium