Pathological keratinisation in the conjunctival epithelium of Sjögren's syndrome.
Our previous gene expression analysis suggested that conjunctival epithelial cells of Sjögren's syndrome (SS) are inclined to hyper-proliferation and keratinisation status. The goal of this study is to elucidate whether such pathological situations really exist in the conjunctival epithelium of SS. Also, involvement of inflammatory cytokines in this disease was investigated. Conjunctival tissues or cells obtained from 12 SS patients and 13 normal subjects were subjected to indirect immunostaining to analyse expression of transglutaminase 1 (TGase1), involucrin, keratins 1, 4, 10 and 13. The number of proliferative cells was also analysed by immunostaining of Ki67 antigen. Additionally, changes in gene expression of TGase1 and involucrin after stimulation by IL-1 or IFN-gamma were quantified by real-time RT-PCR. TGase1 and involucrin were up-regulated in the conjunctival epithelium of SS patients. Although not statistically significant, Ki67 positive proliferative cells were slightly increased in SS patients. IFN-gamma stimulation significantly up-regulated TGase1 and unexpectedly repressed involucrin gene expression. IL-1 did not render any significant changes in the expression of these genes. These results suggest the existence of pathological keratinisation in the conjunctival epithelium of SS and also support our hypothesis that inflammatory cytokines may be involved in the ocular surface pathological changes in SS.
Hirai
Namiko
N
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kawasaki
Satoshi
S
Tanioka
Hidetoshi
H
Connon
Che J
CJ
Yamasaki
Kenta
K
Yokoi
Norihiko
N
Komuro
Aoi
A
Kinoshita
Shigeru
S
D000368:Aged; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D003228:Conjunctiva / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004848:Epithelium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D007633:Keratins / Q000032:analysis / Q000235:genetics; D008875:Middle Aged; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012859:Sjogren's Syndrome / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018709:Statistics, Nonparametric; D011503:Transglutaminases / Q000032:analysis; D015854:Up-Regulation
D015415:Biomarkers; D006684:HLA-DR Antigens; D007375:Interleukin-1; D016209:Interleukin-8; D011498:Protein Precursors; C032253:involucrin; D007633:Keratins; D007371:Interferon-gamma; D011503:Transglutaminases; C105804:transglutaminase 1