Modulation of conjunctival goblet cell function by inflammatory cytokines.

L Contreras-Ruiz,D A Dartt,M A Shatos,S Masli,A Ghosh-Mitra

doi:10.1155/2013/636812

L Contreras-Ruiz, D A Dartt + Show 3 more

Open Access

https://doi.org/10.1155/2013/636812

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Abstract

Ocular surface inflammation associated with Sjögren's syndrome is characterized by a loss of secretory function and alteration in numbers of mucin secreting goblet cells. Such changes are a prominent feature of ocular surface inflammatory diseases and are attributed to inflammation; however, the exact effect of the inflammatory cytokines on conjunctival goblet cell function remains largely unknown. In this study, we developed a primary culture of mouse goblet cells from conjunctival tissue and evaluated the effects on their function by inflammatory cytokines detected in the conjunctiva of mouse model of Sjögren's syndrome (Thrombospondin-1 deficient mice). We found that apoptosis of goblet cells was primarily induced by TNF-α and IFN-γ. These two cytokines also inhibited mucin secretion by goblet cells in response to cholinergic stimulation, whereas IL-6 enhanced such secretion. No changes in secretory response were detected in the presence of IL-13 or IL-17. Goblet cells proliferated to varying degrees in response to all the tested cytokines with the greatest response to IL-13 followed by IL-6. Our results therefore reveal that inflammatory cytokines expressed in the conjunctiva during an ocular surface disease directly disrupt conjunctival goblet cell functions, compromising the protective function of tears, thereby contributing to ocular surface damage.

Highlights

Mucin-secreting goblet cells are widely distributed throughout mammalian mucosal surfaces, such as the gastrointestinal, urogenital, and respiratory tracts, where they play a key role in hydrating, lubricating, and clearing pathogens from the underlying epithelium [1]
To determine if the spontaneous ocular surface inflammation noted in TSP-1 deficient mice involves Th2 cytokines, we examined conjunctival expression of the transcription factor GATA-3, an essential mediator of these cytokines
Together these results suggest involvement of Th2-mediated pathology in the ocular surface inflammation in TSP-1 null mice similar to that reported by others in s syndrome (SS)

Summary

Introduction

Mucin-secreting goblet cells are widely distributed throughout mammalian mucosal surfaces, such as the gastrointestinal, urogenital, and respiratory tracts, where they play a key role in hydrating, lubricating, and clearing pathogens from the underlying epithelium [1]. It is known that IL-13 is involved in lung goblet cell hyperplasia and mucus hypersecretion [10], while IFN-γ inhibited IL-13-induced goblet cell hyperplasia in a mouse model of airway inflammation [11] and it is a potent inhibitor of mucin secretion in a human colonic goblet cell line [12]. We have previously described extensively an autoiummune SS-associated ocular phenotype in Thrombospondin-1 (TSP-1) deficient mice that resembles the changes detectable in SS patients [16] These mice spontaneously and progressively develop inflammation in the conjunctiva, with appearance of inflammatory infiltrates, tissue expression of Th1 and Th17 inflammatory cytokines, along with the development of inflammatory T cell effectors in their draining lymph nodes [17]. Our results reveal that inflammation can directly disrupt conjunctival goblet cell functions resulting in an altered tear composition with a compromised protective function, which contributes to ocular surface damage

Materials and Methods

MUC5AC Secretion

Results

Discussion

Conclusion