title: Increased ribonuclease expression reduces inflammation and prolongs survival in TLR7 transgenic mice.
abstract: TLR7 activation is implicated in the pathogenesis of systemic lupus erythematosus. Mice that overexpress TLR7 develop a lupus-like disease with autoantibodies and glomerulonephritis and early death. To determine whether degradation of the TLR7 ligand RNA would alter the course of disease, we created RNase A transgenic (Tg) mice. We then crossed the RNase Tg to TLR7 Tg mice to create TLR7 × RNase double Tg (DTg) mice. DTg mice had a significantly increased survival associated with reduced activation of T and B lymphocytes and reduced kidney deposition of IgG and C3. We observed massive hepatic inflammation and cell death in TLR7 Tg mice. In contrast, hepatic inflammation and necrosis were strikingly reduced in DTg mice. These findings indicate that high concentrations of serum RNase protect against immune activation and inflammation associated with TLR7 stimulation and that RNase may be a useful therapeutic strategy in the prevention or treatment of inflammation in systemic lupus erythematosus and, possibly, liver diseases.
authors: Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors: Xizhang
authors: X
authors: Sun
authors: Alice
authors: A
authors: Wiedeman
authors: Nalini
authors: N
authors: Agrawal
authors: Thomas H
authors: TH
authors: Teal
authors: Lena
authors: L
authors: Tanaka
authors: Kelly L
authors: KL
authors: Hudkins
authors: Charles E
authors: CE
authors: Alpers
authors: Silvia
authors: S
authors: Bolland
authors: Matthew B
authors: MB
authors: Buechler
authors: Jessica A
authors: JA
authors: Hamerman
authors: Jeffrey A
authors: JA
authors: Ledbetter
authors: Denny
authors: D
authors: Liggitt
authors: Keith B
authors: KB
authors: Elkon
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics* / Q000276:immunology*; D053595:Embryonic Stem Cells; D006505:Hepatitis / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012259:Ribonuclease, Pancreatic / Q000097:blood / Q000235:genetics* / Q000502:physiology; D013154:Spleen / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016019:Survival Analysis; D051199:Toll-Like Receptor 7 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics* / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D012259:Ribonuclease, Pancreatic
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