Modulation of renal disease in MRL/lpr mice by pharmacologic inhibition of inducible nitric oxide synthase

Reilly, Christopher M.; Farrelly, Libby W.; Viti, Dana; Redmond, Shakisha; Hutchison, Florence N.; Ruiz, Phil; Manning, Pam; Connor, Jane R.; Gilkeson, Gary S.

doi:10.1046/j.1523-1755.2002.00230.x

Cited by 54 publications

(49 citation statements)

References 44 publications

(5 reference statements)

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“…These concentrations are within the therapeutic range used in inflammatory diseases (19). Also, concentrations of L-NIL up to 1 mg͞ml do not alter systemic blood pressure in normal rats (19,20), confirming that L-NIL under these conditions does not affect constitutive NOS activity. For POD4 and POD6, grafts were arrested and flushed with cold University of Wisconsin solution, minced, and frozen in liquid nitrogen.…”

Section: Methodsmentioning

confidence: 82%

Non-heme iron protein: A potential target of nitric oxide in acute cardiac allograft rejection

Pieper

Halligan

Hilton

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Section: Methodsmentioning

confidence: 82%

Non-heme iron protein: A potential target of nitric oxide in acute cardiac allograft rejection

Pieper

Halligan

Hilton

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Mesangial cells, such as macrophages, produce nitric oxide (NO), superoxide, and other inflammatory mediators in response to LPS, IFN-c and IL1b. [20][21][22] We and others [23][24][25][26] have reported iNOS expression in renal tissue of lupus patients and evidence of nitrated proteins in kidneys from MRL/lpr mice. In addition to NO, other inflammatory mediators released by mesangial cells have a pathogenic role in lupus (i.e.…”

Section: Mrl/mpj-fasmentioning

confidence: 99%

Epigallocatechin-3-gallate (EGCG) attenuates inflammation in MRL/lpr mouse mesangial cells

et al. 2010

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Epigallocatechin-3-gallate (EGCG), a bioactive component of green tea, has been reported to exert anti-inflammatory effects on immune cells. EGCG is also shown to activate the metabolic regulator, adenosine 5'-monophosphate-activated protein kinase (AMPK). Reports have also indicated that EGCG inhibits the immune-stimulated phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. The PI3K/Akt/mTOR pathway has been implicated in mesangial cell activation in lupus. Mesangial cells from MRL/lpr lupus-like mice are hyper-responsive to immune stimulation and overproduce nitric oxide (NO) and other inflammatory mediators when stimulated. In our current studies, we sought to determine the mechanism by which EGCG attenuates immune-induced expression of pro-inflammatory mediators. Cultured mesangial cells from MRL/lpr mice were pre-treated with various concentrations of EGCG and stimulated with lipopolysaccharide (LPS)/interferon (IFN)-c. EGCG activated AMPK and blocked LPS/ IFN-c-induced inflammatory mediator production (iNOS expression, supernatant NO and interleukin-6). Interestingly, EGCG attenuated inflammation during AMPK inhibition indicating that the anti-inflammatory effect of EGCG may be partially independent of AMPK activation. Furthermore, we found that EGCG effectively inhibited the immune-stimulated PI3K/Akt/mTOR pathway independently of AMPK, by decreasing phosphorylation of Akt, suggesting an alternate mechanism for EGCG-mediated anti-inflammatory action in mesangial cells. Taken together, these studies show that EGCG attenuated inflammation in MRL/lpr mouse mesangial cells via the PI3K/Akt/mTOR pathway. Our findings suggest a potential therapeutic role for the use of EGCG to regulate inflammation and control autoimmune disease.

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“…A subset of animals was treated with the specific inducible nitric oxide synthase (iNOS) inhibitor N6-(1-iminoethyl)-L-lysine (L-NIL) (Alexis Biochemicals, Grün-berg, Germany), which was added to the drinking water at 1 mg/ml until sacrifice (39,51) and given i.p. (0.1 mg/kg in sterile PBS) as a loading dose at the time of surgery.…”

Section: Preparation Of Pcwmentioning

confidence: 99%

Pneumococcal Cell Wall-Induced Meningitis Impairs Adult Hippocampal Neurogenesis

Hoffmann¹,

Mahrhofer²,

Rueter³

et al. 2007

Infect Immun

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Bacterial meningitis is a major infectious cause of neuronal degeneration in the hippocampus. Neurogenesis, a continuous process in the adult hippocampus, could ameliorate such loss. Yet the high rate of sequelae from meningitis suggests that this repair mechanism is inefficient. Here we used a mouse model of nonreplicative bacterial meningitis to determine the impact of transient intracranial inflammation on adult neurogenesis. Experimental meningitis resulted in a net loss of neurons, diminished volume, and impaired neurogenesis in the dentate gyrus for weeks following recovery from the insult. Inducible nitric oxide synthase (iNOS) immunoreactivity was prominent in microglia in nonproliferating areas of the dentate gyrus and hilus region after meningitis induction. Treatment with the specific iNOS inhibitor N6-(1-iminoethyl)-L-lysine restored neurogenesis in experimental meningitis. These data suggest that local central nervous system inflammation in and of itself suppresses adult neurogenesis by affecting both proliferation and neuronal differentiation. Repair of cognitive dysfunction following meningitis could be improved by intervention to interrupt these actively suppressive effects.

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Modulation of renal disease in MRL/lpr mice by pharmacologic inhibition of inducible nitric oxide synthase

Abstract: These results indicate that specific inhibition of iNOS blocks the development of pathologic renal disease in MRL/lpr mice.

Cited by 54 publications

References 44 publications

Non-heme iron protein: A potential target of nitric oxide in acute cardiac allograft rejection

Non-heme iron protein: A potential target of nitric oxide in acute cardiac allograft rejection

Epigallocatechin-3-gallate (EGCG) attenuates inflammation in MRL/lpr mouse mesangial cells

Pneumococcal Cell Wall-Induced Meningitis Impairs Adult Hippocampal Neurogenesis

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