Characterization of serum cytokines and circulating microRNAs that are predicted to regulate inflammasome genes in cutaneous leishmaniasis patients

Mendonça, Lucilla Silva Oliveira; Santos, Jaqueline Marques; Kaneto, Carla Martins; Carvalho, Luciana Debortoli de; Lima-Santos, Jane; Augusto, Danillo G.; Carvalho, Silvia Maria Santos; Soares-Martins, Jamária Adriana Pinheiro; Silva, Alexandre de Almeida e

doi:10.1016/j.exppara.2020.107846

Cited by 18 publications

(11 citation statements)

References 49 publications

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“…[36] identi ed bta-miR-185 targeting ve genes including MLLT3, DYRK1B and NPR2. A few other studies have demonstrated the involvement of bta-miR-223 in bovine mastitis host immune response [37,32], but also in other immune responses to lung infection, bacterial peritonitis, and cutaneous leishmaniasis [38][39][40][41]. The other two miRNA identi ed in our study, bta-mir-149-5p and bta-miR-874, have been associated with fat levels in beef cattle [42,43].…”

Section: Discussionsupporting

confidence: 59%

Regulatory Network of MiRNAs, IncRNAs, Transcription Factors and Target Genes Associated With Immune Response in Bovine Mastitis

Tucker¹,

Salazar²,

Ayoola³

et al. 2021

Preprint

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Background: Bovine mastitis is a mammary gland infectious disease caused by a variety of pathogens with a devasting economic impact worldwide. Pre- and post-transcriptional modifications, including transcription factors (TFs), altering gene expression are emerging foci of disease studies, with minimal studies revealing the importance of non-coding transcripts, like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). We hypothesize TFs, lncRNAs and miRNAs can modulate the immune response in bovine mastitis and can potentially serve as disease biomarkers and/or drug targets.Methods: With computational analyses, we aimed to identify candidate bovine mastitis genes and construct the networks of miRNA, lncRNA and TFs regulating the gene’s mRNA, affecting disease pathogenesis. Experimentally validated genes associated with bovine mastitis were obtained through an extensive search for significantly mentioned genes, utilizing several databases. Prediction of miRNA and lncRNA binding bovine mastitis candidate genes were performed through several algorithms and software that relied on base pair complementation, evolutionary conservation, and thermodynamic stability of binding regions. Combined interactome network of lncRNAs, miRNAs, TFs and immune gene targets were constructed.Results: Sixteen of 923 genes were found to be highly significant in bovine mastitis disease pathway including, CD4, IL-10, IFNγ, IL-4, TLR4, TNFα, and CD14. Remarkably, we found six miRNAs, two being bta-miR-223 and bta-miR-24-3p, to bind to several targets. Eight out of 22 lncRNA, such as NONBTAT027932.1 and XR_003029725.1, were identified as regulatory elements that target the genes based on the normalized binding free energies ranging from -0.1774 to -2.875. Similarly identified were 17 TFs, including JUN and CREB. Our functional and pathway analyses revealed several pathways like lipopolysaccharide-mediated signaling pathway, regulation of chemokine (C-X-C motif) ligand 2 production and regulation of IL-23 production among others. Conclusions: The overarching interactome in this study is the first of its kind regarding bovine mastitis, deserving further in vitro/in vivo explication for specific molecular regulatory mechanisms during bovine mastitis immune response, which could lay the foundation for development of disease markers and therapeutic intervention.

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Section: Discussionsupporting

confidence: 59%

Regulatory Network of MiRNAs, IncRNAs, Transcription Factors and Target Genes Associated With Immune Response in Bovine Mastitis

Tucker¹,

Salazar²,

Ayoola³

et al. 2021

Preprint

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“…In addition, the effects of miR‐223‐3p mimic on the expressions of IL‐1β and TNF‐α in MSU‐induced FLSs were further reversed by NLRP3 over‐expression. Inflammation and the formation of mature IL‐1β and cleaved caspase‐1 together contributed to pyroptosis according to the report [30]. The study illustrated that activated NLRP3 recruited the adaptor protein ASC and aggregated to form an inflammasome complex.…”

Section: Discussionmentioning

confidence: 75%

MiR-223-3p inhibits inflammation and pyroptosis in monosodium urate-induced rats and fibroblast-like synoviocytes by targeting NLRP3

Tian

Zhou

Xiang

et al. 2021

Clinical and Experimental Immunology

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Summary Down‐regulated miR‐223‐3p was found in rheumatoid arthritis. This study aimed to further explore the level and role of miR‐223‐3p in gout arthritis (GA). After monosodium urate (MSU)‐induced GA rat and fibroblast‐like synoviocytes (FLSs) models were established, the rat paw volume and gait score were documented and the FLSs were transfected with miR‐223‐3p mimic/inhibitor or NLR family pyrin domain containing 3 (NLRP3) over‐expression plasmids. The MiR‐223‐3p target was found through bioinformatics and the dual‐luciferase reporter. The rat joint pathological damage was observed by hematoxylin and eosin staining. The levels of interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α and articular elastase in rats were detected by enzyme‐linked immunosorbent assay (ELISA). The viability and pyroptosis of FLSs were detected by methyl thiazolyl tetrazolium (MTT) and flow cytometry. The expressions of miR‐223‐3p, NLRP3, cleaved caspase‐1, IL‐1β, apoptosis‐associated speck‐like protein (AS) and cleaved N‐terminal gasdermin D (GSDMD) in FLSs or rat synovial tissues were detected by reverse transcription–quantitative polymerase chain reaction (RT‐qPCR), immunofluorescence, Western blot or immunohistochemistry analysis. MSU increased the paw volume, gait score, inflammation in synovial tissues and increased the levels of IL‐1β, TNF‐α and articular elastase in rats. MSU decreased the viability and increased the pyroptosis of FLSs, up‐regulated the expression of NLRP3, ASC, cleaved caspase‐1, cleaved N‐terminal GSDM, and IL‐1β, and down‐regulated miR‐223‐3p expression in synovial tissues of rat joints and FLSs. MiR‐223‐3p mimic reversed the effect of MSU on lowering cell viability, increasing pyroptosis in FLSs, while miR‐223‐3p inhibitor further enhanced the effect of MSU on FLSs. NLRP3 was a target of miR‐223‐3p. Also, NLRP3 over‐expression reversed the effects of miR‐223‐3p on MSU‐induced FLSs. MiR‐223‐3p inhibited pyroptosis in MSU‐induced rats and FLSs by targeting NLRP3.

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“…Ma et al 36 identi ed bta-miR-185 targeting ve genes including MLLT3, DYRK1B and NPR2. Other studies have demonstrated the involvement of bta-miR-223 in bovine mastitis immune response 32,37 , but also in other immune responses to lung infection, bacterial peritonitis, and cutaneous leishmaniasis [38][39][40][41] . The other two miRNAs identi ed in our study, bta-mir-149-5p and bta-miR-874, have been associated with fat levels in beef cattle 42,43 .…”

Section: Discussionmentioning

confidence: 99%

Regulatory Network of miRNA, lncRNA, Transcription Factor and Target Immune Response Genes in Bovine Mastitis

Morenikeji

Tucker

Salazar

et al. 2021

Preprint

View full text Add to dashboard Cite

Pre- and post-transcriptional modifications of gene expression are emerging as foci of disease studies, with some studies revealing the importance of non-coding transcripts, like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). We hypothesize that TFs, lncRNAs and miRNAs can modulate the immune response in bovine mastitis and potentially serve as disease biomarkers and/or drug targets. With computational analyses, we identified candidate genes potentially regulated by miRNAs and lncRNAs base pair complementation and thermodynamic stability of binding regions. Remarkably, we found six miRNAs, two being bta-miR-223 and bta-miR-24-3p, to bind to several targets. NONBTAT027932.1 and XR_003029725.1, were identified to target several genes. Functional and pathway analyses revealed lipopolysaccharide-mediated signaling pathway, regulation of chemokine (C-X-C motif) ligand 2 production and regulation of IL-23 production among others. The overarching interactome deserves further in vitro/in vivo explication for specific molecular regulatory mechanisms during bovine mastitis immune response and could lay the foundation for development of disease markers and therapeutic intervention.

show abstract

Characterization of serum cytokines and circulating microRNAs that are predicted to regulate inflammasome genes in cutaneous leishmaniasis patients

Cited by 18 publications

References 49 publications

Regulatory Network of MiRNAs, IncRNAs, Transcription Factors and Target Genes Associated With Immune Response in Bovine Mastitis

Regulatory Network of MiRNAs, IncRNAs, Transcription Factors and Target Genes Associated With Immune Response in Bovine Mastitis

MiR-223-3p inhibits inflammation and pyroptosis in monosodium urate-induced rats and fibroblast-like synoviocytes by targeting NLRP3

Regulatory Network of miRNA, lncRNA, Transcription Factor and Target Immune Response Genes in Bovine Mastitis

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