Beneficial effect of magnolol on lupus nephritis in MRL/lpr mice by attenuating the NLRP3 inflammasome and NF-κB signaling pathway: A mechanistic analysis

Huang, Feng; Zhang, Ruiyun; Song, Lei

doi:10.3892/mmr.2017.7154

Cited by 13 publications

(11 citation statements)

References 36 publications

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“…Previous research found that the nF-κB pathway participates in ln progression (40,41). in the present study, the expression of nF-κB-related proteins in the renal tissues of LN mice was significantly decreased by treatment with pcdna-c1q, indicating that c1q inhibited the nF-κB pathway in these tissues.…”

Section: Discussionsupporting

confidence: 59%

Complement 1q protects MRL/lpr mice against lupus nephritis via inhibiting the nuclear factor-κB pathway

et al. 2020

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lupus nephritis (ln) is a kidney disorder that is a critical cause of mortality in patients with systemic lupus erythematosus. The present study aimed to explore the protective role of complement component 1q (c1q) on ln and the underlying mechanism involving the nuclear factor (nF)-κB singling pathway. Mrl/lpr mice served as the ln mouse model, and pcdna-c1q was injected into ln mice to determine the role of c1q. c1q mrna expression was detected using reverse transcription-quantitative Pcr. urine protein and blood urea nitrogen (Bun) levels were measured, and the histological damage index was determined using H&e staining. eliSa was used to measure the levels of tumor necrosis factor-α (TnF-α), interleukin (il)-1β, il-6, anti-c1q and anti-double stranded dna (dsdna). cd68-and Ki67-positivity were detected using immunofluorescence, and nF-κB-related protein expression was examined using western blotting. c1q mrna expression was downregulated in renal tissues of ln mice. overexpression of c1q decreased urine protein, Bun levels and the histological damage index in ln mice. The levels of TnF-α, il-1β, il-6, anti-c1q and anti-dsdna in renal tissues of ln mice were also reduced after pcdna-c1q treatment. additionally, overexpression of c1q decreased the cd68-and Ki67-positivity in glomeruli and attenuated the expression of nF-κB-related proteins. Phorbol 12-myristate 13-acetate, an nF-κB pathway activator, reversed the inhibitory effect of C1q on inflammation, macrophage infiltration and mesangial cell (MC) proliferation in renal tissues of ln mice. Thus, it was demonstrated that C1q ameliorated inflammation and macrophage infiltration and decreased Mc proliferation in renal tissues of ln mice by inhibiting the nF-κB pathway.

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Section: Discussionsupporting

confidence: 59%

Complement 1q protects MRL/lpr mice against lupus nephritis via inhibiting the nuclear factor-κB pathway

et al. 2020

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“…TNF-α and its receptors are involved in the pathogenesis of autoimmune diseases, and TNF-α has both the effects of controlling autoimmunity and promoting inflammation [40]. TNF-α contributes to the pathogenesis of LN as it promotes the activation and differentiation of macrophages, and its levels are increased in active LN and correlate with disease activity [41]. IL-17 has the potential to induce the production of additional inflammatory cytokines and chemokines and to promote the recruitment of inflammatory cells, such as monocytes and neutrophils, to the inflamed organ; additionally, it is involved in the activation of many proinflammatory pathways [42].…”

Section: Discussionmentioning

confidence: 99%

1,25-dihydroxyvitamin D3 ameliorates lupus nephritis through inhibiting the NF-κB and MAPK signalling pathways in MRL/lpr mice

Liu

Zhao

et al. 2022

BMC Nephrol

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Background Lupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus (SLE). However, the aetiology and pathogenesis of LN remain unknown. 1,25-dihydroxyvitamin D3 [1,25-(OH)2-VitD3] is the active form of vitamin D, and it has been shown to perform important functions in inflammatory and immune-related diseases. In this study, we investigated the time-dependent effects of 1,25-dihydroxyvitamin D3 and explored the underlying mechanism in MRL/lpr mice, a well-studied animal model of LN. Methods Beginning at 8 weeks of age, 24-h urine samples were collected weekly to measure the levels of protein in the urine. We treated female MRL/lpr mice with 1,25-dihydroxyvitamin D3 (4 μg/kg) or 1% DMSO by intraperitoneal injection twice weekly for 3 weeks beginning at the age of 11 weeks. The mice were separately sacrificed, and serum and kidney samples were collected at the ages of 14, 16, 18, and 20 weeks to measure creatinine (Cr) levels, blood urea nitrogen (BUN) levels, histological damage, immunological marker (A-ds DNA, C1q, C3, IgG, IgM) levels, and inflammatory factor (TNF-α, IL-17, MCP-1) levels. Furthermore, the nuclear factor kappa B (NF-κB) and the mitogen-activated protein kinase (MAPK) signalling pathways were also assessed to elucidate the underlying mechanism. Results We found that MRL/lpr mice treated with 1,25-dihydroxyvitamin D3 displayed significantly attenuated LN. VitD3-treated mice exhibited significantly improved renal pathological damage and reduced proteinuria, BUN, SCr, A-ds DNA antibody and immune complex deposition levels (P < 0.05) compared with untreated MRL/lpr mice. Moreover, 1,25-dihydroxyvitamin D3 inhibited the complement cascade, inhibited the release of proinflammatory cytokines, such as TNF-α, IL-17, and MCP-1, and inhibited NF-κB and MAPK activation (P < 0.05). Conclusion 1,25-dihydroxyvitamin D3 exerts a protective effect against LN by inhibiting the NF-κB and MAPK signalling pathways, providing a potential treatment strategy for LN. Interestingly, the NF-κB and MAPK signalling pathways are time-dependent mediators of LN and may be associated with lupus activity.

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“…TNF-αand its receptors are involved in the pathogenesis of autoimmune diseases and TNF-α has both effects of checking autoimmunity and fostering in ammation (33). TNF-α contributes to the pathogenesis of LN as it promotes the activation and differentiation of macrophages, and its levels are increased in active LN and correlate with disease activity (34). IL-17 has a potential to induce the production of additional in ammatory cytokines and chemokines and to promote recruitment of in ammatory cells such as monocytes and neutrophils to the in amed organ, being involved in the activation of many proin ammatory pathways (35).…”

Section: Discussionmentioning

confidence: 99%

1,25-dihydroxyvitamin D3 Ameliorates Lupus Nephritis Through Inhibiting NF-κB and MAPKs Signaling Pathways in MRL/lpr Mice

Zhao

et al. 2021

Preprint

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Background: Lupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus (SLE). However, the etiology and pathogenesis of LN remain unknown. 1,25-dihydroxyvitamin D3（1,25-(OH)2-VitD3）is the active form of vitamin D, which has been known to have important functions in inflammation and immune diseases. In this study, we investigated Its protective effects and underlying mechanism in MRL/lpr mice, a well-studied animal model for lupus.Methods: At the age of 11 weeks, forty-eight MRL/lpr mice were randomly divided into two groups with 24 mice per group: the VitD3-treated group and control group. Mice in the VitD3-treated group received 4μg/kg 1,25-dihydroxyvitamin D3 in 1％ dimethyl sulfoxide (DMSO) intraperitoneal injection twice a week for 3 weeks (mice were executed at 0,2,4,6 weeks after treatment); mice in the control group treated with intraperitoneal injection of 1% DMSO for 3 weeks (mice were executed at 0,2,4,6 weeks after injections). The mice were sacrificed and the serum and kidney samples were collected respectively at planned intervals. Then the skin lesions, histological changes, inflammatory factors (TNF-α, IL-17) and immunological markers (A-ds DNA, C3, IgG, IgM) with time were analyzed between the groups. Furthermore, the NF-κB and MAPKs signaling pathways were also detected to explicate the underlying mechanism. Results: Compared to the control group, mice in the VitD3-treated group showed less skin lesions, less kidney injury, lower serum anti-ds DNA antibody, lower inflammatory cytokines TNF-α, IL-17 and higher serum complement C3; they also had less deposition of IgG, IgM and C3 within glomeruli. Moreover, the expressions of NF-κB and MAPKs signaling pathways were decreased, while those levels were increased with time.Conclusion: This study shows that 1,25-dihydroxyvitamin D3 exerts a protective effect against lupus nephritis via regulating the NF-κB and MAPKs signaling pathways, which will be developed as a potential agent for the treatment of Lupus nephritis. And the relationship between lupus activity and NF-kB and MAPKs signaling pathways with time was revealed.

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Beneficial effect of magnolol on lupus nephritis in MRL/lpr mice by attenuating the NLRP3 inflammasome and NF-κB signaling pathway: A mechanistic analysis

Cited by 13 publications

References 36 publications

Complement 1q protects MRL/lpr mice against lupus nephritis via inhibiting the nuclear factor-κB pathway

Complement 1q protects MRL/lpr mice against lupus nephritis via inhibiting the nuclear factor-κB pathway

1,25-dihydroxyvitamin D3 ameliorates lupus nephritis through inhibiting the NF-κB and MAPK signalling pathways in MRL/lpr mice

1,25-dihydroxyvitamin D3 Ameliorates Lupus Nephritis Through Inhibiting NF-κB and MAPKs Signaling Pathways in MRL/lpr Mice

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