The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune disease: increased nitric oxide production and nitric oxide synthase expression in MRL-lpr/lpr mice, and reduction of spontaneous glomerulonephritis and arthritis by orally administered NG-monomethyl-L-arginine.

Weinberg, J. Brice; Granger, Donald L.; Pisetsky, David S.; Seldin, Michael F.; Misukonis, Mary A.; Mason, S. Nicholas; Pippen, Anne M.; Ruiz, Phillip; Wood, Edgar R.; Gilkeson, Gary S.

doi:10.1084/jem.179.2.651

Cited by 422 publications

(269 citation statements)

References 58 publications

(67 reference statements)

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“…After incubation, culture supernatants were collected and used for an NO assay. NO formation was determined as the stable production of nitrite (NO 2 -) in culture supernatants using Griess reagent [53].…”

Section: No Assaymentioning

confidence: 99%

Treponemal glycoconjugate inhibits Toll‐like receptor ligand‐induced cell activation by blocking LPS‐binding protein and CD14 functions

2003

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Spirochetes are well-known as causative agents of various chronic infectious diseases. Glycolipids of small-sized Treponema spirochetes have been shown to exhibit immunostimulating activities. In this study, we found that a glycoconjugate preparation obtained from Treponema medium (Tm-Gp), an intermediate-sized oral Treponema seen in subgingival plaque from patients with chronic periodontal diseases, diminished the LPS-induced activation of a human monocytic cell line, while TNF- § -induced activation was unaffected. NF-‹ B activation in Ba/F3 cells expressing murine Toll-like receptor (TLR) 4 and MD-2 was inhibited by Tm-Gp in a CD14/LPS-binding protein (LBP)-dependent manner when stimulated with LPS or its active center lipid A but not when stimulated with Taxol. Tm-Gp blocked the binding of LPS to immobilized CD14 and LBP and inhibited nitric oxide (NO) production by a murine M ¤ cell line following stimulation with peptidoglycan and LPS in the presence of FBS, while NO production in response poly (I:C) RNA or CpG DNA remained unaffected. The inhibitory effects of Tm-Gp seem to be attributable to the lipophilic portion of the glycoconjugate. These results indicate that T. medium contains a glycoconjugate possessing an inhibitory effect on TLR-mediated cell activation through interaction with LBP and CD14.

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Section: No Assaymentioning

confidence: 99%

Treponemal glycoconjugate inhibits Toll‐like receptor ligand‐induced cell activation by blocking LPS‐binding protein and CD14 functions

2003

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“…Increased levels could merely reflect underlying inflammation. Nevertheless, there is increased production of NO during the course of the murine MRL/lpr and NZB/W models of lupus and in human SLE (265)(266)(267). Moreover, elevated levels of endothelial cell iNOS, serum nitrite and peroxynitrite levels correlate with measures of disease activity and titers of dsDNA antibodies (267,268).…”

Section: Nitric Oxide and Inducible Nitric Oxide Synthasementioning

confidence: 99%

The pathophysiology of photosensitivity in lupus erythematosus

Orteu

Sontheimer

Dutz

2001

Photoderm Photoimm Photomed

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“…In addition to glomerulonephritis, MRL-lpr mice also develop arthritis, vasculitis, and lymphoproliferation (18). We previously demonstrated that spontaneous immune complex glomerulonephritis and arthritis in MRL-lpr mice was significantly decreased by NMMA administration early in disease (19). These mice were given an arginine-free diet to prevent arginine from competitively inhibiting NMMA uptake in macrophages (20).…”

Section: Introductionmentioning

confidence: 99%

“…These mice were given an arginine-free diet to prevent arginine from competitively inhibiting NMMA uptake in macrophages (20). Control MRL-lpr mice in these experiments, on the arginine-free diet, developed less pathologic disease than historical controls, suggesting dietary arginine restriction alone may alter disease expression (19).…”

Section: Introductionmentioning

confidence: 99%

Effect of Late Modulation of Nitric Oxide Production on Murine Lupus

Oates

Ruiz

Alexander

et al. 1997

Clinical Immunology and Immunopathology

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MRL/MpJ-Fas lpr (MRL-lpr) and New Zealand Black/White (NZB/W) mice develop spontaneous autoimmune disease characterized by autoantibody production and glomerulonephritis that progresses in parallel with increasing systemic nitric oxide (NO) production. A pre-viously published study from our laboratory indicated that oral administration of the nitric oxide synthase inhibitor N G -monomethyl-L-arginine (NMMA) before the onset of clinical disease significantly decreased renal and joint pathology in MRL-lpr mice. To characterize the effect of late modulation of NO production in murine SLE, we administered oral NMMA and/or restricted dietary arginine after disease onset in two murine models of SLE. When receiving combined NMMA and arginine restriction, MRL-lpr mice had reduced joint pathology scores and NZB/W mice had lower renal pathology scores than control mice. These results indicate that modulating NO production after the onset of disease diminishes disease severity in two models of SLE, although not as effectively as treating before disease onset.

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The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune disease: increased nitric oxide production and nitric oxide synthase expression in MRL-lpr/lpr mice, and reduction of spontaneous glomerulonephritis and arthritis by orally administered NG-monomethyl-L-arginine.

Cited by 422 publications

References 58 publications

Treponemal glycoconjugate inhibits Toll‐like receptor ligand‐induced cell activation by blocking LPS‐binding protein and CD14 functions

Treponemal glycoconjugate inhibits Toll‐like receptor ligand‐induced cell activation by blocking LPS‐binding protein and CD14 functions

The pathophysiology of photosensitivity in lupus erythematosus

Effect of Late Modulation of Nitric Oxide Production on Murine Lupus

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