title: Up-regulation of cytokine mRNA, adhesion molecule proteins, and MHC class II proteins in salivary glands of TGF-beta1 knockout mice: MHC class II is a factor in the pathogenesis of TGF-beta1 knockout mice.
abstract: Mice homozygous for a disrupted TGF-beta1 allele develop multiple lymphoproliferative disorders similar to those seen in the pseudolymphoma of Sjögren's syndrome. At 2 wk of age, these TGF-beta1 mutant mice begin to develop wasting syndrome and die at around 4 to 5 wk of age. We studied salivary glands from symptomatic mutant mice >14 days of age. Reverse transcriptase-PCR analysis showed up-regulation of proinflammatory cytokine genes such as IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, and IFN-gamma in these mutant mice. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1), and MHC class II as well as CD4-positive T lymphocyte infiltration was detected by immunostaining. To elucidate the role of MHC class II, salivary glands from TGF-beta1/MHC class II double knockout mice were used to investigate the expression of adhesion molecules and MHC class II. In spite of the existence of basal intercellular adhesion molecule-1 expression on vessels, there was neither MHC class II expression, enhanced vascular cell adhesion molecule-1 expression, nor lymphocytic infiltration in the salivary glands. These results suggest that MHC class II plays a significant role in the pathogenesis of TGF-beta1 mutant mice. Although the mechanism that initiates multiple inflammatory diseases in these mice remains unclear, the context reported here would provide insight into the immunopathology of Sjögren's syndrome.
authors.affiliation: Audie L. Murphy Memorial Veterans Hospital and Department of Medicine, University of Texas Health Science Center, San Antonio 78284, USA.
authors.forename: T
authors.initials: T
authors.lastname: Nakabayashi
authors.forename: J J
authors.initials: JJ
authors.lastname: Letterio
authors.forename: A G
authors.initials: AG
authors.lastname: Geiser
authors.forename: L
authors.initials: L
authors.lastname: Kong
authors.forename: N
authors.initials: N
authors.lastname: Ogawa
authors.forename: W
authors.initials: W
authors.lastname: Zhao
authors.forename: T
authors.initials: T
authors.lastname: Koike
authors.forename: G
authors.initials: G
authors.lastname: Fernandes
authors.forename: H
authors.initials: H
authors.lastname: Dang
authors.forename: N
authors.initials: N
authors.lastname: Talal
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D012469:Salivary Glands / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta