Abstract
Innate immunity of the corneal epithelium is conferred by proteinaceous secretions from the epithelium and associated lacrimal and meibomian glands. Lacritin, an eye-specific protein with anti-microbial, cytoprotective and wound-healing properties, predominantly secreted by lacrimal glands, is absent in conditions such as Dry eye and Keratitis. In view of the biological significance of lacritin in human eye, we investigated its role in human corneal epithelial (HCE) cells during lipopolysaccharide (LPS)-induced infection. LPS-challenged HCE cells demonstrated apoptosis-mediated cell death and elevated lacritin levels. The LPS-induced cell death is alleviated with exogenous supplementation of recombinant lacritin. This cytoprotective effect of lacritin is mediated through Cyclooxygenase-2 (COX-2). This study is the first to highlight the protective role of lacritin and mechanism of its action during bacterial infection of cornea in vitro.
Highlights
Innate immune response to ocular infection involves several factors such as lysozyme, lipocalin, lactoferrin, mucins, surfactant protein D, secretory IgA, cytokeratin-derived antimicrobial peptides, β -defensins, constitutively-expressed tear proteins and numerous uncharacterized secretory proteins from lacrimal and meibomian glands and from the corneal and conjunctival epithelium that are activated upon infection[6,7,8,9,10,11]
Cell death induced by lower doses of LPS (< 1 μ g/ml) was not significantly different from the control; 50% cell death was observed at a dose of 10 μ g/ml LPS
Corneal epithelium in synergy with tear fluid and its soluble factors plays a crucial role in innate immunity during infection[26]
Summary
Innate immune response to ocular infection involves several factors such as lysozyme, lipocalin, lactoferrin, mucins, surfactant protein D, secretory IgA, cytokeratin-derived antimicrobial peptides, β -defensins, constitutively-expressed tear proteins and numerous uncharacterized secretory proteins from lacrimal and meibomian glands and from the corneal and conjunctival epithelium that are activated upon infection[6,7,8,9,10,11]. Lacritin, is the only molecule with mitogenic potential[17] and anti-microbial activity[18,19], which is down regulated in Dry eye[14], Keratitis[20], and various other pathological conditions associated with ocular tissue[12,16]. Lacritin induces tear secretion[21,22], relieves epithelial stress[23], offers cytoprotection[24], and promotes corneal wound-healing[25]. This multifunctional eye-specific factor with its potential role(s) in corneal integrity has immense therapeutic value. We obtained the cues to decipher the underlying mechanism by which lacritin might confer innate immunity to the cells
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