PURPOSE: During inflammation of the ocular surface, increased proinflammatory 
cytokines depress tear protein secretion, suggesting that a decline in lacrimal 
cell function contributes to dry eye. Lacritin, a glycoprotein secreted from 
lacrimal acinar cells, may function as an autocrine factor to stimulate tear 
protein secretion. The purpose of the present experiment was to investigate 
lacritin-induced protein secretion in normal and cytokine-pretreated 
(inflammation model) monkey acinar cells.
METHODS: Acinar cells from monkey lacrimal glands were cultured with or without 
tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ). Protein 
secretion was induced by lacritin or carbachol (Cch, positive control). Proteins 
were detected and identified by immunoblotting and immunocytochemistry. 
Intracellular Ca(2+) was measured with the fluorophore Calcium-4, and cell 
damage was determined by LDH leakage into the culture medium.
RESULTS: In cultured monkey acinar cells, lacritin stimulated tear protein 
secretion in normal cells without elevating intracellular Ca(2+). In contrast, 
Cch elevated intracellular Ca(2+) and release of tear proteins. This contrast 
suggested an alternate, calcium-independent mechanism for lacritin-induced 
protein secretion. TNF-α plus IFN-γ caused LDH leakage from sensitive human 
corneal epithelial cells, but even higher doses of TNF-α plus IFN-γ did not 
cause LDH leakage from monkey acinar cells, suggesting a higher tolerance 
against these cytokines. In cytokine-treated acinar cells, lacritin stimulated 
protein secretion as much as that in normal cells. In contrast, Cch-induced 
elevation of Ca(2+) and release of proteins were depressed by cytokines.
CONCLUSIONS: Lacritin might be a useful biotechnology-based treatment agent 
against ocular surface diseases where endogenous lacritin is inadequate.