Interaction of IFN-γ with cholinergic agonists to modulate rat and human goblet cell function

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-gamma), a Th1 cytokine increased in dry eye, alters goblet cell function. Goblet cells from rat and human conjunctiva were cultured. Changes in intracellular [ Ca2+] ([Ca2+](i)), high molecular weight glycoconjugate secretion, and proliferation were measured after stimulation with IFN-gamma with or without the cholinergic agonist carbachol. IFN-gamma itself increased [ Ca2+](i) in rat and human goblet cells and prevented the increase in [ Ca2+](i) caused by carbachol. Carbachol prevented IFN-gamma-mediated increase in [ Ca2+](i). This cross-talk between IFN-gamma and muscarinic receptors may be partially due to use of the same Ca2+ (i) reservoirs, but also from interaction of signaling pathways proximal to the increase in [ Ca2+](i). IFN-gamma blocked carbachol-induced high molecular weight glycoconjugate secretion and reduced goblet cell proliferation. We conclude that increased levels of IFN-gamma in dry eye disease could explain the lack of goblet cells and mucin deficiency typically found in this pathology. IFN-gamma could also function similarly in respiratory and gastrointestinal tracts.