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.
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.
Nakabayashi
T
T
Audie L. Murphy Memorial Veterans Hospital and Department of Medicine, University of Texas Health Science Center, San Antonio 78284, USA.
Letterio
J J
JJ
Geiser
A G
AG
Kong
L
L
Ogawa
N
N
Zhao
W
W
Koike
T
T
Fernandes
G
G
Dang
H
H
Talal
N
N
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
D015815:Cell Adhesion Molecules; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta