Enhanced expression of NLRP3 inflammasome-related inflammation in peripheral blood mononuclear cells in Sjögren's syndrome

Kim, Seong-Kyu; Choe, Jung‐Yoon; Lee, Geon Ho

doi:10.1016/j.cca.2017.09.019

Cited by 37 publications

(19 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased expression of NLRP3, PYCARD, CASPASE-1 and IL-1β does occur in conditions such as atherosclerosis (31), Sjögren's syndrome (32) and preeclampsia (33), so it is intriguing that we found no increases in basal expression of these genes in gout patients, given the importance of IL-1B in the disease process in gout. Of note, expression of NLRP3 was relatively low compared to both IL-1B and CASP1 consistent with the requirement for TLR-induced transcriptional priming and translation of NLRP3 prior to oligomerization and activation of the NLRP3 inflammasome (15).…”

Section: Discussionmentioning

confidence: 91%

Precipitation of Soluble Uric Acid Is Necessary forIn VitroActivation of the NLRP3 Inflammasome in Primary Human Monocytes

Alberts

Barber²,

Sacre³

et al. 2019

J Rheumatol

View full text Add to dashboard Cite

Objective. To investigate the effects of soluble uric acid (UA) on expression and activation of the NODlike receptor (NLR) pyrin domain containing protein 3 (NLRP3) inflammasome in human monocytes to elucidate the role of hyperuricemia in the pathogenesis of gout.Methods. Primary human monocytes and the THP-1 human monocyte cell line were used to determine the effects of short-and long-term exposure to UA on activation of the NLRP3 inflammasome and subsequent interleukin-1β (IL-1β) secretion by enzyme linked immunosorbent assay (ELISA) and cell-based assays. Expression of key NLRP3 components in monocytes from patients with a history of gout were analysed by quantitative PCR.Results. Precipitation of UA was required for the activation of the NLRP3 inflammasome and subsequent release of IL-1β in human monocytes. Neither monosodium urate (MSU) crystals nor soluble UA had any effect on activation of the transcription factor, NF-κB. Prolonged exposure of monocytes to soluble UA did not alter these responses. However, both MSU crystals and soluble UA did result in a 2-fold increase in reactive oxygen species (ROS). Gout patients (n=15) had significantly elevated serum UA concentrations compared to healthy individuals (n=16), yet secretion of IL-1β and expression of NLRP3 inflammasome components in monocytes isolated from these patients were not different from healthy controls. Conclusion.Despite recent reports indicating that soluble UA can prime and activate the NLRP3 inflammasome in human peripheral blood mononuclear cells (PBMCs), precipitation of soluble UA into MSU crystals is essential for in vitro NLRP3 signalling in primary human monocytes.

show abstract

Section: Discussionmentioning

confidence: 91%

Precipitation of Soluble Uric Acid Is Necessary forIn VitroActivation of the NLRP3 Inflammasome in Primary Human Monocytes

Alberts

Barber²,

Sacre³

et al. 2019

J Rheumatol

View full text Add to dashboard Cite

show abstract

“…Interestingly, NLRP3 is activated by 5′ uncapped nucleic acids that may belong to pathogens such as viruses or damaged cells (e.g., cancer cells) and nucleic acids and ribonucleoproteins can activate AIM2 inflammasome and contribute to the progression of SLE [73]. It has been shown that NLRP3 and AIM2 activation is increased in the PBMCs and salivary gland-infiltrating macrophages of SS patients [74, 75] and that activation of the inflammasome in SS epithelial cells is directly associated with the likelihood of developing a B cell lymphoma [37]. According to the results of a fascinating ex vivo study on minor salivary gland biopsies of SS patients, it is likely that an aberrant methylation of LINEs1 inside epithelial cells and the concomitant expression of open reading frame 1/p40 protein would induce their recognition by TLR7 and TLR8, activate the NF- κ B pathway, and generate a type I IFN signature [76].…”

Section: Resultsmentioning

confidence: 99%

Microbial Agents as Putative Inducers of B Cell Lymphoma in Sjögren’s Syndrome through an Impaired Epigenetic Control: The State-of-The-Art

Talotta

Sarzi‐Puttini

Atzeni

2019

Journal of Immunology Research

View full text Add to dashboard Cite

Introduction Understanding the mechanisms underlying the pathogenesis of Sjögren's syndrome (SS) is crucially important in order to be able to discriminate the steps that lead to B cell transformation and promptly identify the patients at risk of lymphomagenesis. The aim of this narrative review is to describe the evidence concerning the role that infections or dysbiosis plays in the epigenetic control of gene expression in SS patients and their possible involvement in B cell lymphomagenesis. Materials and Methods We searched the PubMed and Google Scholar databases and selected a total of 92 articles published during the last 25 years that describe experimental and clinical studies of the potential associations of microbiota and epigenetic aberrations with the risk of B cell lymphoma in SS patients. Results and Discussion The genetic background of SS patients is characterized by the hyperexpression of genes that are mainly involved in regulating the innate and adaptive immune responses and oncogenesis. In addition, salivary gland epithelial cells and lymphocytes both have an altered epigenetic background that enhances the activation of proinflammatory and survival pathways. Dysbiosis or chronic latent infections may tune the immune response and modify the cell epigenetic machinery in such a way as to give B lymphocytes an activated or transformed phenotype. It is also worth noting that transposable integrated retroelements may participate in the pathogenesis of SS and B cell lymphomagenesis by inducing DNA breaks, modulating cell gene expression, or generating aberrant transcripts that chronically stimulate the immune system. Conclusions Microorganisms may epigenetically modify target cells and induce their transcriptome to generate an activated or transformed phenotype. The occurrence of lymphoma in more than 15% of SS patients may be the end result of a combination of genetics, epigenetics, and dysbiosis or latent infections.

show abstract

“…For instance, Kim et al indicated that NOD-like receptor protein 3 (NLRP3) inflammasome was upregulated in pSS patients and were associated with the disease activity. [ 25 ] Vakrakou et al further found that NLRP3 inflammasome was highly associated with impaired DNA degradation in pSS. [ 26 ] Dupire et al illustrated that highly expressed high mobility group box-1 (HMGB1) levels were highly correlated with disease activity of pSS.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of progranulin correlated with serum soluble Oxford 40 ligand in primary Sjögren's syndrome

Guo²,

Sun³

et al. 2020

Medicine

View full text Add to dashboard Cite

The present study aimed to investigate the association between the expressions of serum progranulin (PGRN) and serum soluble Oxford 40 ligand (sOX40L) and determine their clinical significances in primary Sjögren's syndrome (pSS). The present study included a total of 68 patients with pSS and 50 healthy controls. Demographic data and clinical basic information were collected. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum levels of PGRN, sOX40L and interleukins. Spearman's correlation coefficient and Mann–Whitney U test were used to determine the correlation between PGRN, and sOX40L and the association between PGRN and sOX40L and disease activity and disease severity. Serum interleukin (IL)-4, IL-6, IL-10, PGRN, and sOX40L levels were significantly higher in pSS patients as compared to the healthy controls. A positive correlation was observed between PGRN and sOX40L. Patients with elevated levels of PGRN or sOX40L exhibited higher disease activity compared to those with lower levels. Patients with III to IV stages of pSS or multiple system damage showed higher serum levels of PGRN and sOX40L. Elevated serum PGRN, and sOX40L levels were relevant with disease activity and severity in patients with pSS.

show abstract

Enhanced expression of NLRP3 inflammasome-related inflammation in peripheral blood mononuclear cells in Sjögren's syndrome

Cited by 37 publications

References 29 publications

Precipitation of Soluble Uric Acid Is Necessary forIn VitroActivation of the NLRP3 Inflammasome in Primary Human Monocytes

Precipitation of Soluble Uric Acid Is Necessary forIn VitroActivation of the NLRP3 Inflammasome in Primary Human Monocytes

Microbial Agents as Putative Inducers of B Cell Lymphoma in Sjögren’s Syndrome through an Impaired Epigenetic Control: The State-of-The-Art

Clinical significance of progranulin correlated with serum soluble Oxford 40 ligand in primary Sjögren's syndrome

Contact Info

Product

Resources

About