title: High expression of interleukin-1beta in the corneal epithelium of MRL/lpr mice is under the control of their genetic background.
abstract: MRL/Mp mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop polyarthritis, sialoadenitis and dacryoadenitis, resembling rheumatoid arthritis (RA), and also corneal involvement such as keratopathy and scleritis, which is a major complication in RA patients. In this study, we found that the expression levels of IL-1beta and MMP-1 mRNAs in cornea were high in both MRL/lpr and MRL/Mp-+/+ strains of mice at an age younger than when they develop any inflammatory lesions. This was not true of other inbred strains, even those bearing the lpr gene, and also not of (NZB x NZW) F1 lupus mice. There was no significant difference in the expression of IL-1alpha and TGFbeta in cornea in these strains. Using crosses between MRL/lpr and C3H/HeJ-lpr/lpr (C3H/lpr) mice, at least the expression of IL-1beta was found to be under the control of the MRL genetic background, likely with a recessive mode of inheritance. Considering that IL-1beta in cornea was detected particularly in the epithelial layer, the high expression of IL-1beta in cornea is most likely involved in the genetic predisposition for corneal involvement and possibly also for arthritis in an MRL strain of mice.
authors.affiliation: Department of Ophthalmology, Ehime University School of Medicine, Shizukawa, Shigenobu-cho, Ehime, Japan. masahiro.okamoto@santen.co.jp
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.forename: M
authors.initials: M
authors.lastname: Takagi
authors.forename: M
authors.initials: M
authors.lastname: Kutsuna
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
authors.forename: M
authors.initials: M
authors.lastname: Nishihara
authors.forename: M C
authors.initials: MC
authors.lastname: Zhang
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: M
authors.initials: M
authors.lastname: Sakanaka
authors.forename: S
authors.initials: S
authors.lastname: Okamoto
authors.forename: M
authors.initials: M
authors.lastname: Nose
authors.forename: Y
authors.initials: Y
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D019573:Epithelium, Corneal / Q000276:immunology*; D017353:Gene Deletion; D015870:Gene Expression; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D007150:Immunohistochemistry / Q000379:methods; D007375:Interleukin-1 / Q000032:analysis* / Q000235:genetics; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000235:genetics; D019014:fas Receptor / Q000235:genetics*
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019014:fas Receptor; D020781:Matrix Metalloproteinase 1