Regulation of leukotriene B4 secretion by human corneal, conjunctival, and meibomian gland epithelial cells.
OBJECTIVE
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.


CONCLUSIONS
When induced by appropriate stimuli, LTB4 production may have a role in the generation of inflammation in ocular surface disease.
Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford St, Boston, MA 02114, USA.
Afsun
A
Sahin
Wendy R
WR
Kam
Raheleh Rahimi
RR
Darabad
Kimberly
K
Topilow
David A
DA
Sullivan
D000209:Acute-Phase Proteins / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D002460:Cell Line; D003228:Conjunctiva / Q000187:drug effects* / Q000378:metabolism; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008537:Meibomian Glands / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000494:pharmacology; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D016718:Arachidonic Acid; D002352:Carrier Proteins; D013196:Dihydrotestosterone; D007975:Leukotriene B4; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein