Regulation of Leukotriene B4Secretion by Human Corneal, Conjunctival, and Meibomian Gland Epithelial Cells

OBJECTIVES: To test the hypotheses that lipopolysaccharide (LPS) stimulates leukotriene B4 (LTB4) production in human ocular surface and adenexal cells, arachidonic acid duplicates the stimulatory effect of LPS, LPS-binding protein potentiates LPS-induced LTB4 secretion, and dihydrotestosterone attenuates the immune effect of LPS. METHODS: Immortalized human corneal, conjunctival, and meibomian gland epithelial cells were cultured in the presence or absence of fetal bovine serum and were exposed to vehicle, LPS, LPS plus LPS-binding protein, arachidonic acid, or dihydrotestosterone. Culture media were processed for the LTB4 analysis. RESULTS: Lipopolysaccharide stimulates time-dependent secretion of LTB4 by human corneal, conjunctival, and meibomian gland epithelial cells. This effect, which we could not detect with arachidonic acid, is potentiated by exposure to LPS-binding protein. This potentiation, in turn, is significantly reduced by cellular treatment with dihydrotestosterone. CONCLUSIONS: Ocular epithelial cells have the ability to generate LTB4 in response to LPS exposure. This proinflammatory process is modulated by LPS-binding protein and by dihydrotestosterone. CLINICAL RELEVANCE: When induced by appropriate stimuli, LTB4 production may have a role in the generation of inflammation in ocular surface disease.