Sialoglyco-Conjugate Abnormalities, IL-6 Trans-Signaling and Anti-Ganglioside Immune Response—Potential Interferences in Lupus Nephritis Pathogenesis

Ene, Corina-Daniela; Penescu, Mircea; Nicolae, Ilinca

doi:10.3390/diagnostics11061129

Cited by 6 publications

(4 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inflammation, oxidative imbalance, immune activation, autoantibody production, overstimulation of type 1 interferon (IFN), generation of inflammatory mediators, and tissue damage are fundamental contributors to SLE pathogenesis [ 1 , 2 , 3 ]. A series of experimental data have suggested that reactions mediated by inducible synthase of nitric oxide (NOS2 or iNOS) could be involved in the pathogenesis of SLE [ 4 , 5 , 6 , 7 , 8 ]. An inflammatory stimulus triggers iNOS production, further orchestrating inflammation, angiogenesis, and tissue fibrosis [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Skin and mucous involvement includes skin rashes, photosensitivity, mucosal ulcers, and alopecia. Patients with SLE frequently develop lupus nephritis (LN), which can evolve to end-stage renal disease [ 5 , 7 , 8 ]. NL development is multifactorial, involving genetic susceptibility, environmental factors, and systemic inflammation [ 4 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Inflammatory Profile Orchestrated by Inducible Nitric Oxide Synthase in Systemic Lupus Erythematosus

Ene

Nicolae

2023

JPM

Self Cite

View full text Add to dashboard Cite

(1) Background: The pathogenesis of systemic lupus erythematosus (SLE) involves complicated and multifactorial interactions. Inducible nitric oxide synthase overactivation (iNOS or NOS2) could be involved in SLE pathogenesis and progression. This study explored the relationship between NOS2-associated inflammation profiles and SLE phenotypes. (2) Methods: We developed a prospective, case control study that included a group of 86 SLE subjects, a group of 73 subjects with lupus nephritis, and a control group of 60 people. Laboratory determinations included serum C reactive protein (CRP–mg/L), enzymatic activity of NOS2 (U/L), serum levels of inducible factors of hypoxia 1 and 2 (HIF1a–ng/mL, HIF2a–ng/mL), vascular endothelial growth factor VEGF (pg/mL), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9–ng/mL), thrombospondin 1 (TSP-1–ng/mL), and soluble receptor of VEGF (sVEGFR–ng/mL). (3) Results: CRP, NOS2, HIF-1a, HIF-2a, VEGF, MMP-2, and MMP-9 were significantly increased, while TSP-1 and sVEGFR were decreased in the SLE and lupus nephritis groups compared with the control group. The variations in these biomarkers were strongly associated with the decrease in eGFR and increase in albuminuria. (4) Conclusions: The inflammatory phenotype of SLE patients, with or without LN, is defined by NOS2 and hypoxia over-expression, angiogenesis stimulation, and inactivation of factors that induce resolution of inflammation in relation with eGFR decline.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Inflammatory Profile Orchestrated by Inducible Nitric Oxide Synthase in Systemic Lupus Erythematosus

Ene

Nicolae

2023

JPM

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition to the C1q and IL-6, mounting evidence has recently suggested that Wnt/β-catenin signaling was involved in the pathogenesis of SLE [20][21][22][23] . In this regard, the Wnt/β-catenin pathway induces the stability of β-catenin and transfers into the nucleus upon the activation, ultimately facilitating the expression of genes involved in cell proliferation, survival, differentiation and migration [24] .…”

Section: Introductionmentioning

confidence: 99%

Aberrant expression of C1q, IL-6 and β-catenin in class VI lupus nephritis

Xue,

Min,

Zhu

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: complement component C1q, interleukin-6 (IL-6) and β-catenin have been implicated in the pathogenesis of lupus nephritis (LN). However, their correlation with the pathological progression and type of LN remain unclear. Methods: the concentrations of C1q, IL-6 and β-catenin were evaluated in plasma, urine and kidney tissues in LN patients, non-LN systemic lupus erythematosus (SLEn) patients, and healthy cohorts, as well as C57BL/6, IL-6-/-, MRL-Fas/lpr and MRL-Fas/lprIL-6-/- mice. Results: more abundant plasma C1q, IL-6 and urine C1q proteins were determined in LN and SLEn patients compared to healthy cohorts. Of note, the concentration of IL-6 and β-catenin in both plasma and urine, and plasma C1q was even higher in LN patients relative to SLEn subjects. Moreover, positive correlations were determined for C1q and β-catenin proteins between plasma and urine in LN patients. Of importance, both plasma and urine β-catenin, and urine IL-6 were significantly increased in patients with class VI LN patients relative to those who suffered from class I LN. Immunohistochemical study further uncovered that the abundant IL-6 and β-catenin proteins were deposited in both renal glomeruli and tubules, while the C1q was only found in renal glomeruli of patients with class IV LN. Consistent with the clinical findings, experimental studies in MRL-Fas/lprIL-6-/- mice also showed a decreased β-catenin in urine, C1q and β-catenin in kidney tissues of MRL-Fas/lprIL-6-/- mice compared with MRL-Fas/lpr mice. Interestingly, mice with deficiency of IL-6 exhibited less degrees of proteinuria and histological lesions, and reduced serum anti-double-stranded DNA (anti-dsDNA) antibody and sizes of spleen and inguinal node, as compared with MRL-Fas/lpr and C57/BL6 control mice. Conclusions: these data suggest a strong correlation among IL-6, C1q and β-catenin in the pathogenesis of type VI LN in SLE patients, indicating that they may be valuable biomarkers for nephrologists to guide treatment and predict prognosis among these patients.

show abstract

“…Increased sialylation in melanoma cells could represent an event associated with the progression of cutaneous melanoma [ 17 ]. Sialoglycoconjugates may promote processes that are involved in the modulation of host immune and inflammatory responses [ 37 ]. Sialylation, manifested as the overexpression of TSA, LSA, and orosomucoid, has been shown to be an early, well-expressed event in the initial stages of clear cell renal cell carcinoma [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Sialylation Changes in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma Patients

Tampa

Nicolae

Mitran

et al. 2021

JPM

Self Cite

View full text Add to dashboard Cite

Cutaneous squamous cell carcinoma (cSCC), a malignant proliferation of the cutaneous epithelium, is the second most common skin cancer after basal cell carcinoma (BCC). Unlike BCC, cSCC exhibits a greater aggressiveness and the ability to metastasize to any organ in the body. Chronic inflammation and immunosuppression are important processes linked to the development of cSCC. The tumor can occur de novo or from the histological transformation of preexisting actinic keratoses (AK). Malignant cells exhibit a higher amount of sialic acid in their membranes than normal cells, and changes in the amount, type, or linkage of sialic acid in malignant cell glycoconjugates are related to tumor progression and metastasis. The aim of our study was to investigate the sialyation in patients with cSCC and patients with AK. We have determined the serum levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), beta-galactoside 2,6-sialyltransferase I (ST6GalI), and neuraminidase 3 (NEU3) in 40 patients with cSCC, 28 patients with AK, and 40 healthy subjects. Data analysis indicated a significant increase in serum levels of TSA (p < 0.001), LSA (p < 0.001), ST6GalI (p < 0.001), and NEU3 (p < 0.001) in the cSCC group compared to the control group, whereas in patients with AK only the serum level of TSA was significantly higher compared to the control group (p < 0.001). When the cSCC and AK groups were compared, significant differences between the serum levels of TSA (p < 0.001), LSA (p < 0.001), ST6GalI (p < 0.001) and NEU3 (p < 0.001) were found. The rate of synthesis of sialoglycoconjugates and their rate of enzymatic degradation, expressed by the ST6GalI/NEU3 ratio, is 1.64 times lower in the cSCC group compared to the control group (p < 0.01) and 1.53 times lower compared to the AK group (p < 0.01). The tumor diameter, depth of invasion, and Ki67 were associated with higher levels of TSA and LSA. These results indicate an aberrant sialylation in cSCC that correlates with tumor aggressiveness.

show abstract

Sialoglyco-Conjugate Abnormalities, IL-6 Trans-Signaling and Anti-Ganglioside Immune Response—Potential Interferences in Lupus Nephritis Pathogenesis

Cited by 6 publications

References 50 publications

The Inflammatory Profile Orchestrated by Inducible Nitric Oxide Synthase in Systemic Lupus Erythematosus

The Inflammatory Profile Orchestrated by Inducible Nitric Oxide Synthase in Systemic Lupus Erythematosus

Aberrant expression of C1q, IL-6 and β-catenin in class VI lupus nephritis

Serum Sialylation Changes in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma Patients

Contact Info

Product

Resources

About