IFN-gamma: regulation of nitric oxide in the P. aeruginosa-infected cornea.
OBJECTIVE
BALB/c mice are resistant to Pseudomonas aeruginosa (P. aeruginosa) keratitis and bacterial killing/stasis requires nitric oxide (NO). NO regulation in the cornea is unknown and was tested in this model.


METHODS
Nitrite detection, IFN-gamma-knockout mice, TNF-alpha neutralization, ELISA, aminoguanidine (AG) treatment, MPO, and plate counts were done.


RESULTS
Evidence shows (i) without IFN-gamma, nitrite levels are elevated, (ii) neutralization of TNF-alpha does not change nitrite levels, and (iii) absence of IFN-alpha and reduced NO synergistically increases disease progress and upregulates pro-inflammatory cytokines, PMN number, and bacterial load.


CONCLUSIONS
IFN-gamma regulates NO levels, and synergistic interaction between the two regulates disease outcome in resistant mice.
McClellan
Sharon A
SA
Department of Anatomy & Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Lighvani
Shahrzad
S
Hazlett
Linda D
LD
D000818:Animals; D015169:Colony Count, Microbial; D003315:Cornea / Q000378:metabolism / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D015818:Eye Infections, Bacterial / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D007371:Interferon-gamma / Q000502:physiology*; D007634:Keratitis / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D011552:Pseudomonas Infections / Q000378:metabolism* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*
D016207:Cytokines; D004791:Enzyme Inhibitors; D006146:Guanidines; D009573:Nitrites; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; C004479:pimagedine