NLRP2 Regulates Proinflammatory and Antiapoptotic Responses in Proximal Tubular Epithelial Cells

Rossi, Marianna Nicoletta; Pascarella, Antonia; Licursi, Valerio; Caiello, Ivan; Taranta, Anna; Rega, Laura Rita; Levtchenko, Elena; Emma, Francesco; Benedetti, Fabrizio; Prencipe, Giusi

doi:10.3389/fcell.2019.00252

Cited by 35 publications

(30 citation statements)

References 57 publications

(64 reference statements)

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“…Finally, our findings also showed a differential expression of some genes that play a role in the immune response including the NLRP2, which is involved in the suppression of the NF-κB signaling pathway leading to the modulation of the inflammatory response [29]. In addition, it is also considered as an important component of the inflammasome, which is a multiprotein intracellular complex, essential for the detection of the pathogenic microorganisms and activation of the pro-inflammatory cytokines including interleukin-1β (IL-1β) and IL-18 [30,31]. Similarly, PTGDR2, which we also found to be differentially expressed between both genders, is believed to be essential for the pro-inflammatory cytokines induction and found to play a role in asthma pathogenesis [32].…”

Section: Discussionmentioning

confidence: 99%

The Molecular Basis of Gender Variations in Mortality Rates Associated with the Novel Coronavirus (COVID-19) Outbreak

Hachim¹,

Hachim²,

Talaat³

et al. 2020

Preprint

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Since the outbreak of the novel coronavirus disease (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact between different subpopulations. Emerging evidence from different parts of the world showed significantly poor outcome among males compared to female patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for a more effective and targeted response to the outbreak. For that reason, here we try to investigate the molecular basis of the gender variations in mortality rates related to COVID-19 infection. To achieve this, we used our in-house pipeline to process publicly available lung transcriptomic data from 141 females compared to 286 males. After excluding Y specific genes, our results showed a shortlist of 73 genes that are differentially expressed between the two groups. Our results showed downregulation of a group of genes that are involved in the regulation of hydrolase activity including (AGTR1, CHM, DDX3X, FGFR3, SFRP2, and NLRP2), which is also believed to be essential for lung immune response and antimicrobial activity in the lung tissues in males compared to females. In contrast, our results showed an upregulation of angiotensin II receptor type 1 (AGTR1), a member of the renin-angiotensin system (RAS) that plays a role in angiotensin-converting enzyme 2 (ACE2) activity modulation. Interestingly, recent reports and experimental animal models highlight an important role of this receptor in SARS-Coronavirus lung damage as well as pulmonary edema, suggesting a possible role of its blockers like losartan and olmesartan as potential therapeutic options for COVID-19 infection. Finally, our results also showed a differential expression of different genes that are involved in the immune response including the NLRP2 and PTGDR2, further supporting the notion of the sex-based immunological differences. Taken together, our results provide an initial evidence of the molecular mechanisms that might be involved in the differential outcomes observed between both genders during the COVID-19 outbreak. This might be essential for the discovery of new targets and more precise therapeutic options to treat COVID-19 patients from different clinical and epidemiological characteristics with the aim of improving their outcome.

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Section: Discussionmentioning

confidence: 99%

The Molecular Basis of Gender Variations in Mortality Rates Associated with the Novel Coronavirus (COVID-19) Outbreak

Hachim¹,

Hachim²,

Talaat³

et al. 2020

Preprint

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“…The canonical (or classical) pathway leads to the activation of the p50/p65 (RelA) or p50/c-Rel heterodimers, while the non-canonical (or alternative) pathway leads to the activation of the p52/RelB heterodimer. The different heterodimers play distinct biological roles, controlling lymphoid organ development, immune activation, and cell survival (44)(45)(46). In healthy cells, NF-κB complexes are retained in the cytoplasm by inhibitory proteins belonging to the IκB family.…”

Section: Nf-κb Among Inflammation Immunity and Cancermentioning

confidence: 99%

Regulation of PD-L1 Expression by NF-κB in Cancer

et al. 2020

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Immune checkpoints are inhibitory receptor/ligand pairs regulating immunity that are exploited as key targets of anti-cancer therapy. Although the PD-1/PD-L1 pair is one of the most studied immune checkpoints, several aspects of its biology remain to be clarified. It has been established that PD-1 is an inhibitory receptor up-regulated by activated T, B, and NK lymphocytes and that its ligand PD-L1 mediates a negative feedback of lymphocyte activation, contributing to the restoration of the steady state condition after acute immune responses. This loop might become detrimental in the presence of either a chronic infection or a growing tumor. PD-L1 expression in tumors is currently used as a biomarker to orient therapeutic decisions; nevertheless, our knowledge about the regulation of PD-L1 expression is limited. The present review discusses how NF-κB, a master transcription factor of inflammation and immunity, is emerging as a key positive regulator of PD-L1 expression in cancer. NF-κB directly induces PD-L1 gene transcription by binding to its promoter, and it can also regulate PD-L1 post-transcriptionally through indirect pathways. These processes, which under conditions of cellular stress and acute inflammation drive tissue homeostasis and promote tissue healing, are largely dysregulated in tumors. Up-regulation of PD-L1 in cancer cells is controlled via NF-κB downstream of several signals, including oncogene- and stress-induced pathways, inflammatory cytokines, and chemotherapeutic drugs. Notably, a shared signaling pathway in epithelial cancers induces both PD-L1 expression and epithelial–mesenchymal transition, suggesting that PD-L1 is part of the tissue remodeling program. Furthermore, PD-L1 expression by tumor infiltrating myeloid cells can contribute to the immune suppressive features of the tumor environment. A better understanding of the interplay between NF-κB signaling and PD-L1 expression is highly relevant to cancer biology and therapy.

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“…The role of kinase B, which then degrade leading to the activation of NF-B. A study has been conducted in Cystinosis patients, which is a disorder characterized by the accumulation of the amino acid cystine within cells that resulted in many organs and tissues damages, has found a high expression of NLRP2 in these patients in the (PTEC) in the kidney [21].…”

Section: Negative Regulation Transcriptional Activitymentioning

confidence: 99%

The Role of Immune-related NLR Pyrin Domain Containing 2 (NLRP2) Gene in the Development and Diseases

Basingab

Alghamdi

Alhazmi

et al. 2021

JPRI

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The Nucleotide-binding oligomerization domain, Leucine-rich Repeat, and Pyrin domain-containing (NLRP) family, including NLR Family Pyrin Domain-Containing 2 (NLRP2) gene, is defined as a critical element in regulating both apoptosis and inflammation. Although the NLRP2 protein involves in stimulating the production of inflammatory cytokines and chemokines in response to pathogens, the expression of NLRP2 gene has been reported in many diseases. Some studies indicated that NLRP2 as a Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB)-positive regulator resulted in the production of NF-κB-driven cytokines. Wherease other studies reported NLRP2 as an NF-κB-negative regulator that limits IκB kinase, an enzyme involved in elucidating the cellular response to inflammation. This literature review has directly evaluated the relation of both the NLRP2 gene and NLRP2 protein in the development and different diseases based on journal articles obtained from databases such as PubMed, Science direct and Medline. Scientific names and symbols of the gene were utilized as keywords for published data from 2003 until 2020. We propose that the overexpression of the NLRP2 gene might result in an inflammatory microenvironment associated with localized or systematic diseases based on; the cells that express this particular gene and the location of the immune responses and the triggered signal transduction pathway.

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NLRP2 Regulates Proinflammatory and Antiapoptotic Responses in Proximal Tubular Epithelial Cells

Cited by 35 publications

References 57 publications

The Molecular Basis of Gender Variations in Mortality Rates Associated with the Novel Coronavirus (COVID-19) Outbreak

The Molecular Basis of Gender Variations in Mortality Rates Associated with the Novel Coronavirus (COVID-19) Outbreak

Regulation of PD-L1 Expression by NF-κB in Cancer

The Role of Immune-related NLR Pyrin Domain Containing 2 (NLRP2) Gene in the Development and Diseases

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