Renal cell apoptosis and proliferation may be linked to nuclear factor–κB activation and expression of inducible nitric oxide synthase in patients with lupus nephritis

Zheng, Ling; Sinniah, Raja; Hsu, Shu-Hui

doi:10.1016/j.humpath.2006.01.002

Cited by 39 publications

(26 citation statements)

References 34 publications

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“…In vivo and in vitro studies have suggested that the transcription factor NF-kB plays a role in tubulointerstitial injury. Indeed, both IHC and SWH demonstrated that the activation of NFkB was related to tubulointerstitial injury and deterioration of renal function [3,22]. These findings were similar to those from our study, which found positive correlations between NF-kB expression (SWH and IHC) and serum creatinine at the time of biopsy as well as NF-kB (SWH) expression and serum creatinine at the end of the follow-up.…”

Section: Discussionsupporting

confidence: 90%

“…In human renal disease, there has not been any histologic evidence of NFkB activation in vascular cells [10,11,17,22]. Although we also failed to find vascular expression of NF-kB by SWH or IHC, our study showed that NF-kB, measured by both SWH and IHC, was correlated with the presence of vascular injury.…”

Section: Discussioncontrasting

confidence: 57%

“…One study showed a correlation between the activation of NF-kB and interstitial infiltration of macrophages in lupus nephritis [22]. In addition, recent studies have suggested that the signaling pathway of NF-kB was involved in the activation of macrophages [21].…”

Section: Discussionmentioning

confidence: 99%

“…Once activated, NF-kB, activates the transcription of target genes involved in inflammation, immunity, apoptosis, cell proliferation and differentiation [8,16]. Using southwestern histochemistry (SWH), some previous studies demonstrated that NF-kB played a pivotal role in proteinuric nephropathy, such as minimal change disease, idiopathic membranous nephropathy, diabetic nephropathy and lupus nephritis [10,11,22]. Indeed, proteins have been shown to activate tubular expression of chemokines, mainly MCP-1, in proximal tubules through an NF-kB-dependent mechanism [6].…”

Section: Introductionmentioning

confidence: 99%

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NF-kB Expression in IgA Nephropathy Outcome

et al. 2011

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Abstract. Some studies have demonstrated the involvement of nuclear factor-kappa B (NF-kB) in the pathogenesis of glomerulonephritis. The aim of our study was twofold: (1) to analyze the prognostic value of NF-kB expression in primary IgA nephropathy (IgAN) and (2) to compare the results of NF-kB expression by immunohistochemistry (IHC) and southwestern histochemistry (SWH). We analyzed 62 patients diagnosed with IgAN from 1987 to 2003. We used monoclonal antibodies to CD68 and mast cell tryptase and polyclonal antibodies to TGF-β1, α-SMA and NF-kB p65. We used SWH for the in situ detection of activated NF-kB. The results showed that NF-kB expression (mainly by SWH) correlated with clinical and histological parameters. An unfavorable clinical course of IgAN was significantly related to tubular NF-kB expression by SWH, but not by IHC. The KaplanMeier curves demonstrated that increased NF-kB expression, which was measured by IHC and SWH, decreased renal survival. In conclusion, the increased expression of NF-kB in the tubular area may be a predictive factor for the poor prognosis of patients with IgAN. Compared with IHC, NF-kB expression determined by SWH was correlated with a larger number of parameters of poor disease outcome.

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Section: Discussionsupporting

confidence: 90%

Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NF-kB Expression in IgA Nephropathy Outcome

et al. 2011

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“…We cannot rule out an effect of CO over the production of other proinflammatory cytokines released by infiltrating myeloid cells or glomerular cells such as podocytes that could also impact kidney function and membranous changes [48,49]. Along these lines, the beneficial consequences of CO treatment could be explained by a blocking effect of CO on different factors that may participate in nephritis pathogenesis in SLE patients and murine models, such as the presence of stromal cell apoptosis [26,50,51]. Accordingly, CO could promote cell survival of endothelial cells, as has been observed with ischaemia and cytostatic drugs [47,52].…”

mentioning

confidence: 99%

Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus

Mackern-Oberti

Obreque

Méndez

et al. 2015

Clinical and Experimental Immunology

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SummarySystemic lupus erythematosus is characterized by the presence of circulating anti-nuclear antibodies (ANA) and systemic damage that includes nephritis, haematological manifestations and pulmonary compromise, among others. Although major progress has been made in elucidating the molecular mechanisms responsible for autoimmunity, current therapies for lupus have not improved considerably. Because the exposure of carbon monoxide (CO) has been shown to display beneficial immunoregulatory properties in different immune-mediated diseases, we investigated whether CO therapy improves lupus-related kidney injury in lupus mice. MRL-Fas lpr lupus mice were exposed to CO and disease progression was evaluated. ANA, leucocyteinfiltrating populations in spleen, kidney and lung and kidney lesions, were measured. CO therapy significantly decreased the frequency of activated B220 1 CD4 2 CD8 2 T cells in kidneys and lungs, as well as serum levels of ANA. Furthermore, we observed that CO therapy reduced kidney injury by decreasing proliferative glomerular damage and immune complexes deposition, decreased proinflammatory cytokine production and finally delayed the impairment of kidney function. CO exposure ameliorates kidney and lung leucocyte infiltration and delays kidney disease in MRLFas lpr lupus mice. Our data support the notion that CO could be explored as a potential new therapy for lupus nephritis.

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Association of serum nitrate and nitrite levels with longitudinal assessments of disease activity and damage in systemic lupus erythematosus and lupus nephritis

Oates¹,

Shaftman²,

Self³

et al. 2007

Arthritis & Rheumatism

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Objective. Reactive intermediate production is an essential component of the innate immune response that is induced during disease activity in murine lupus. This study was undertaken to determine whether a marker of systemic nitric oxide (NO) production correlates with prospectively studied disease activity in human systemic lupus erythematosus (SLE) and lupus nephritis patients.Methods. Eighty-three SLE patients and 40 control subjects were studied longitudinally. The SLE group included 23 patients with lupus nephritis documented by renal biopsy and 26 with a history of lupus nephritis. During each visit, following a 24-hour lownitrate diet, traditional markers of disease activity and damage were determined. Serum nitrate plus nitrite (NOx) levels were determined by chemiluminescence detection.Results. NOx levels were higher in SLE patients than in controls during the first visit. In univariate longitudinal analyses, NOx levels were associated with SLE Disease Activity Index scores. In multivariate analyses, NOx levels were associated with serum levels of C3 and creatinine and the urinary protein:creatinine ratio. Among patients with lupus nephritis, those with proliferative lesions had higher NOx levels, and higher NOx levels were associated with accumulation of renal damage and lack of response to therapy.Conclusion. This is the first study to prospectively demonstrate longitudinal associations between serum NOx levels and markers of SLE and lupus nephritis disease activity. The more pronounced association with proliferative lupus nephritis and with longitudinal response to lupus nephritis therapy provides a rationale for the study of reactive intermediates as biomarkers of disease activity and therapeutic targets in proliferative lupus nephritis.A common feature in the broad phenotype of systemic lupus erythematosus (SLE) is autoantibody production, a function primarily of the acquired immune system (1). However, an inappropriately active innate immune response is implicated in both the initiation and the pathogenic consequences of autoantibody production in SLE. An important antimicrobial factor in the innate immune response is the production of reactive oxygen and nitrogen intermediates (RONI), including superoxide and nitric oxide (NO) (2).In murine models of lupus, NO production has been shown to increase with the progression of renal disease. Pharmacologic inhibition of inducible NO synthase (iNOS) in these models significantly reduced both NO and reactive oxygen intermediate (ROI) production and also reduced inflammatory glomerular lesions, without affecting the deposition of immunoglobulin or complement (2,3). These findings suggest that iNOS activity or products of iNOS such as superoxide and NO contribute to the proliferative glomerular lesions in murine lupus nephritis and that their production is distal to immune complex deposition and complement activation. Cross-sectional studies of NO production in human SLE have demonstrated increased levels of markers of sys-

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Renal cell apoptosis and proliferation may be linked to nuclear factor–κB activation and expression of inducible nitric oxide synthase in patients with lupus nephritis

Cited by 39 publications

References 34 publications

NF-kB Expression in IgA Nephropathy Outcome

NF-kB Expression in IgA Nephropathy Outcome

Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus

Association of serum nitrate and nitrite levels with longitudinal assessments of disease activity and damage in systemic lupus erythematosus and lupus nephritis

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