Effect of interferon on a primary conjunctival epithelial cell model of trachoma.
An in vitro human primary conjunctival epithelial system was adapted to determine if the effects of interferon-gamma (IFN-gamma), as described in cultured cell lines, were applicable to human ocular infection with Chlamydia trachomatis, Primary human epithelial cell cultures were exposed to varying concentrations of IFN-gamma. The treatment resulted in the induction of the tryptophan decyclizing enzyme indolamine 2,3-deoxygenase (IDO) in a dose-dependent manner as determined by assaying the conversion of tryptophan to its metabolites using reversed-phase high-performance liquid chromatography. Little IDO induction occurred in the presence of IFN-alpha or IFN-beta. Catabolism of up to 38% of available tryptophan occurred in IFN-gamma-treated cells in contrast to controls that showed only baseline activity. Cells cultured with IFN-gamma and then infected with an ocular isolate of C. trachomatis (TW-5), had a reduction in the percentage of inclusion-containing cells by over 80% in a dose-dependent manner. Reversal by the addition of exogenous tryptophan substantiated that IFN-gamma-mediated induction of IDO and catabolism of tryptophan were responsible for inhibition of intracellular growth of C. trachomatis.
Department of Ophthalmology, University of Wisconsin, Madison 53705.
P A
PA
Rapoza
S G
SG
Tahija
J P
JP
Carlin
S L
SL
Miller
M L
ML
Padilla
G I
GI
Byrne
D002478:Cells, Cultured; D002692:Chlamydia trachomatis / Q000187:drug effects / Q000254:growth & development; D002851:Chromatography, High Pressure Liquid; D003228:Conjunctiva / Q000187:drug effects* / Q000201:enzymology / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D014141:Trachoma / Q000188:drug therapy*; D014364:Tryptophan / Q000378:metabolism / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000378:metabolism
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007370:Interferon Type I; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase