Spontaneous ocular surface inflammation and goblet cell disappearance in I kappa B zeta gene-disrupted mice.
OBJECTIVE
The ocular surface epithelium is part of the mucosal defense system. Because transcription factor NF-kappa B in mucosal epithelial cells plays a central role in regulating the genes that govern the onset of mucosal inflammatory responses, we examined the role of a regulator of NF-kappa B, I kappa B zeta, in murine ocular surface inflammation.


METHODS
The eyes of I kappa B zeta(-/-) mice were analyzed biomicroscopically and histologically. I kappa B zeta expression in normal mouse cornea and conjunctiva was examined by RT-PCR. The results were compared with those obtained in other tissues by real-time PCR. I kappa B zeta mRNA on the ocular surface and in other mucosal tissues was localized by in situ hybridization.


RESULTS
I kappa B zeta(-/-) mice manifested chronic inflammation, specifically in the ocular surface, but not in other tissues. In normal mice, I kappa B zeta was expressed in a variety of mucosal tissues. The I kappa B zeta transcript was predominantly distributed in the epithelia of these tissues. As inflammatory symptoms progressed on the ocular surface of I kappa B zeta(-/-) mice, inflammatory cells, mainly CD45R/B220(+) and CD4(+) cells, intensely infiltrated the submucosa of the conjunctival epithelia. This infiltration was accompanied by an almost complete loss of goblet cells in the conjunctival epithelia.


CONCLUSIONS
The authors postulate that I kappa B zeta in the ocular surface epithelia negatively regulates the pathologic progression of ocular surface inflammation.
Ueta
Mayumi
M
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan. mueta@ophth.kpu-m.ac.jp
Hamuro
Junji
J
Yamamoto
Masahiro
M
Kaseda
Kazuhiro
K
Akira
Shizuo
S
Kinoshita
Shigeru
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016923:Cell Death; D003231:Conjunctivitis / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000473:pathology; D019573:Epithelium, Corneal / Q000473:pathology; D020397:Goblet Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020672:I-kappa B Proteins / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; D020672:I-kappa B Proteins; C417234:NFKBIZ protein, human; C491366:Nfkbie protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger