Sjögren's syndrome autoantibodies provoke changes in gene expression profiles of inflammatory cytokines triggering a pathway involving TACE/NF-κB

Lisi, Sabrina; Sisto, Margherita; Lofrumento, Dario Domenico; D’Amore, Simona

doi:10.1038/labinvest.2011.190

Cited by 53 publications

(47 citation statements)

References 37 publications

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“…To clarify the mechanisms suspected of mediating the therapeutic effects of RTX, we tested in vitro whether RTX‐mediated pro‐inflammatory protein down‐regulation could be a result of the inhibition of the constitutive activity of the NF‐ κ B pathway in pSS SGEC. Results of our previous studies and those of other authors have shown that pSS SGEC are characterized by persistent NF‐ κ B activation, which could explain the deregulated cytokine production observed in pSS . These reported findings are consistent with those demonstrating that defects in the regulation of NF‐ κ B‐dependent gene expression contribute to a variety of inflammatory and autoimmune diseases, neurological disorders and cancer .…”

Section: Discussionsupporting

confidence: 91%

“…These phenomena may be due to the epithelial activation by cytokines locally produced by the lymphocytic infiltrates, or to intrinsically operating processes that may occur in the epithelia of pSS patients. Evidence from our laboratory had indicated that pSS SGEC, cultured in vitro , are capable of expressing various immune‐response proteins such as cytokines, chemokines and their receptors . Prompted by such protein production, we sought to establish a co‐culture system for the functional assessment of SGEC capacity to interact with lymphoid cells in vitro .…”

Section: Discussionmentioning

confidence: 99%

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Rituximab‐mediated Raf kinase inhibitor protein induction modulates NF‐κB in Sjögren syndrome

et al. 2014

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SummaryPrimary Sj€ ogren syndrome (pSS) is an autoimmune disorder characterized by an epithelial injury surrounded by dense lymphocytic infiltrates. The conditions for the long-term maintenance of human salivary gland epithelial cells from pSS patients and a co-culture system with pSS lymphocytes were used to assess the effect of Rituximab (RTX) on the inflammatory condition and progression in pSS. Quantitative real-time PCR, genes and protein array analysis, Western blot, flow cytometry, small interfering RNA transfection and nuclear factor-jB (NF-jB) DNA binding assays were used as methods. Supporting the benefits of RTX, this study demonstrates that RTX decreases NF-jB activity and interrupts the NF-jB signalling pathway through the up-regulation of the Raf-1 kinase inhibitor protein (RKIP). Over-expression of RKIP down-regulates interleukins, their receptors and the expression of genes encodes proteins that attracted lymphocytes. Silencing of the RKIP gene leads to significantly increased expression and release of pro-inflammatory mediators supporting that RKIP expression could be involved in the suppression of NF-jB activation in pSS salivary gland epithelial cells.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Rituximab‐mediated Raf kinase inhibitor protein induction modulates NF‐κB in Sjögren syndrome

et al. 2014

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“…NFkB activates up-regulated CXCR4, suggesting a role for the CXCR4/CXCL12 signaling axis in diabetic nephropathy [49]. The network also shows NF-kB acting on up-regulated CCR2, a receptor involved in monocyte activation [50], on up-regulated CXCL1, the prototypical neutrophil chemokine [51], on up-regulated CXCL10, a leukocyte chemoattractant [52], and on up-regulated CCL19, a chemokine for dendritic cells and T lymphocytes [53]. NF-kB, activated by IL1R, the receptor for IL-1 [54], acts on up-regulated collagen I gene, a redundant effect mediated by C3a, C5a, and IL-1 [55].…”

Section: Resultsmentioning

confidence: 99%

Renal C3 Complement Component: Feed Forward to Diabetic Kidney Disease

Kelly

Liu²,

Zhang

et al. 2015

Am J Nephrol

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Background: Diabetic nephropathy is the main cause of end-stage renal disease and has reached epidemic proportions. Methods: Comprehensive genomic profiling (RNAseq) was employed in the ZS (F₁ hybrids of Zucker and spontaneously hypertensive heart failure) model of diabetic nephropathy. Controls were lean littermates. Results: Diabetic nephropathy in obese, diabetic ZS was accelerated by a single episode of renal ischemia (DI). This rapid renal decline was accompanied by the activation of the renal complement system in DI, and to a lesser extent in sham-operated diabetic rats (DS). In DI there were significant increases in renal mRNA encoding C3, C4, C5, C6, C8, and C9 over sham-operated lean normal controls (LS). Moreover, mRNAs encoding the receptors for the anaphylatoxins C3a and C5a were also significantly increased in DI compared to LS. The classic complement pathway was activated in diabetic kidneys with significant increases of C1qa, C1qb, and C1qc mRNAs in DI over LS. In addition, critical regulators of complement activation were significantly attenuated in DI and DS. These included mRNAs encoding CD55, decay accelerating factor, and CD59, which inhibit the membrane attack complex. C3, C4, and C9 proteins were demonstrated in renal tubules and glomeruli. The complement RNAseq data were incorporated into a gene network showing interactions among C3-generating renal tubular cells and other immune competent migratory cells. Conclusions: We conclude that local activation of the complement system mediates renal injury in diabetic nephropathy.

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“…Increasing evidence shows that ADAM17 contributes to the cascade release of inflammatory cytokines, such as IL-1β and IL-6, from PBMCs via several inflammationrelated signaling pathways [50][51][52]. In addition, ADAM17-deficient mice exhibits a decreased serum concentrations of pro-inflammation cytokines including IL-1β, IL-10 and IL-6, and is protected from sepsis [19,20,53].…”

Section: Discussionmentioning

confidence: 99%

Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis

Shao

Chen

et al. 2016

Cell Physiol Biochem

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Background: A disintegrin and metalloproteinase 17 (ADAM17) has been confirmed to play a significant role in the pathogenesis of sepsis. However, little is known about the clinical relevance of ADAM17 polymorphisms to sepsis onset and development. Methods: This study analyzed the associations of five ADAM17 promoter polymorphisms (rs55790676, rs12692386, rs11684747, rs1524668 and rs11689958) with sepsis (370 sepsis cases and 400 controls). Genotyping was performed using pyrosequencing and polymerase chain reaction-length polymorphism method. The ADAM17 expression was measured using the real-time PCR method and the concentrations of related cytokines were detected using enzyme-linked immunosorbent assay. Results: No associations were observed between these polymorphisms and sepsis susceptibility, while the rs12692386GA/GG genotypes were overrepresented among the patients with severe sepsis (P=0.002) or septic shock (P=0.0147) compared to those with sepsis subtype, suggesting a susceptible role of rs12692386A>G in the progression of sepsis. Moreover, ADAM17 expression was increased in the sepsis patients with the rs12692386GA/GG genotypes, accompanied by up-regulation of expression of the ADAM17 substrates (TNF-α, IL-6R and CX3CL1) and pro-inflammatory cytokines (IL-1β and IL-6). Conclusion: The present study has provided potentially valuable clinical evidence that the ADAM17 rs12692386 polymorphism is a functional variant that might be used as a relevant risk estimate for the progression of sepsis.

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Sjögren's syndrome autoantibodies provoke changes in gene expression profiles of inflammatory cytokines triggering a pathway involving TACE/NF-κB

Cited by 53 publications

References 37 publications

Rituximab‐mediated Raf kinase inhibitor protein induction modulates NF‐κB in Sjögren syndrome

Rituximab‐mediated Raf kinase inhibitor protein induction modulates NF‐κB in Sjögren syndrome

Renal C3 Complement Component: Feed Forward to Diabetic Kidney Disease

Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis

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