Prostaglandin I2 (PGI2) inhibits Brucella abortus internalization in macrophages via PGI2 receptor signaling, and its analogue affects immune response and disease outcome in mice

Vu, Son Hai; Reyes, Alisha Wehdnesday Bernardo; Huy, Tran Xuan Ngoc; Min, Wongi; Lee, Hu Jang; Kim, Hyun‐Jin; Lee, John Hwa; Kim, Suk

doi:10.1016/j.dci.2020.103902

Cited by 10 publications

(6 citation statements)

References 42 publications

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“…In this GSEA, we found that PTGIS was not enriched at the high expression site as expected, but there were two enrichment peaks, respectively, at the high expression site and the low expression site. This may be due to the different roles of the gene in different diseases; many scholars have found its different roles in different diseases [28][29][30][31][32][33][34][35]. PTGIS plays a positive role in cardiovascular diseases by regulating fatty acid metabolism [29,33,35,36], while it is the opposite in cancer [25,[37][38][39][40][41][42].…”

Section: Discussionmentioning

confidence: 99%

PTGIS May Be a Predictive Marker for Ovarian Cancer by Regulating Fatty Acid Metabolism

Lü

et al. 2023

Computational and Mathematical Methods in Medicine

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Background. Ovarian cancer tends to metastasize to the omentum, which is an organ mainly composed of adipose tissue. Many studies have found that fatty acid metabolism is related to the occurrence and metastasis of cancers. Therefore, it is possible that fatty acid metabolism-related genes (FAMRG) affect the prognosis of ovarian cancer patients. Methods. First, profiles of ovarian cancer and normal ovarian tissue transcriptomes were acquired from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. A LASSO regression predictive model was developed via the “glmnet” R package. The nomogram was created via the “regplot.” Gene Set Variation Analysis (GSVA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses were conducted to determine the FAMRGs’ roles. The percentage of immunocyte infiltration was calculated via CIBERSORT. Using “pRRophetic,” the sensitivity of eight regularly used medications and immunotherapy was anticipated. Results. 125 genes were determined as different expression genes (DEGs). Based on RXRA, ECI2, PTGIS, and ACACB, a prognostic model is created and the risk score is calculated. Analyses of univariate and multivariate regressions revealed that the risk score was a distinct prognostic factor (univariate: HR: 2.855, 95% CI: 1.756-4.739, P < 0.001 ; multivariate: HR: 2.943, 95% CI: 1.800-4.812, P < 0.001 ). The nomogram demonstrated that it properly predicted the 1-year survival rate. The expression of memory B molecular units, follicular helper T molecular units, regulatory T molecular units, and M1 macrophages differed remarkably between the groups at high and low risk ( P < 0.05 ). Adipocytokine signaling pathways, cancer pathways, and degradation of valine, leucine, and isoleucine vary between high- and low-risk populations. The findings of the GO enrichment revealed that the extracellular matrix and cellular structure were the two most enriched pathways. PTGIS, which is an important gene in fatty acid metabolism, was identified as the hub gene. This result was verified in ovarian cancer and ovarian tissues. The connection between the gene and survival was statistically remarkable ( P = 0.015 ). The pRRophetic algorithm revealed that the low-risk group was more adaptable to cisplatin, doxorubicin, 5-fluorouracil, and etoposide ( P < 0.001 ). Conclusion. PTGIS may be an indicator of prognosis and a possible therapeutic target for the therapy of ovarian cancer patients. The fatty acid metabolism of immune cells may be controlled, which has an indirect effect on cancer cell growth.

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Section: Discussionmentioning

confidence: 99%

PTGIS May Be a Predictive Marker for Ovarian Cancer by Regulating Fatty Acid Metabolism

Lü

et al. 2023

Computational and Mathematical Methods in Medicine

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“…Induction of AA production by B. abortus -infected dendritic cells was also reported [ 25 ]. On the other hand, we previously reported that AA had bactericidal effect against B. abortus [ 8 ]. Leukotrienes are formed via LOX pathway initiated by 5-LOX while PG, PC and TX are derived from AA via COX pathway [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, in response to different types of stimuli such as cytokines, PLA2 is activated to produce AA from membrane phospholipids and these free AA can be metabolized to other metabolic by-products by certain enzymes such as COX-2 [ 25 ]. Previously, we showed that COX-2 was significantly expressed in infected bone marrow-derived macrophages (BMDMs) from mice and RAW264.7 cells [ 8 ]. In the present study, inhibiting AA metabolism could be a protective approach against dissemination of B. abortus inside host cells.…”

Section: Discussionmentioning

confidence: 99%

“…AA is obtained from food or via desaturation and chain elongation of linoleic acid (LA) and it is a precursor in the biosynthesis of biologically active FA mediators metabolized by cyclooxygenases (COXs), lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes via phospholipase A2 (PLA2) [ 6 , 7 ]. We previously reported that AA was highly toxic to B. abortus 544 [ 8 ]. AA is converted to unstable endoperoxides by COX from which prostaglandins (PG), prostacyclin (PC) and thromboxanes (TX) are derived [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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The In Vitro and In Vivo Effect of Lipoxygenase Pathway Inhibitors Nordihydroguaiaretic Acid and Its Derivative Tetra-O-methyl Nordihydroguaiaretic Acid againstBrucella abortus544

Reyes

Kim

Huy

et al. 2022

J. Microbiol. Biotechnol.

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This study investigated the contribution of lipoxygenase (LOX) inhibitors, nordihydroguaiaretic acid (NDGA), tetra-O-methyl nordihydroguaiaretic acid (M 4 N) and zileuton (ZIL), and thromboxane A2 (TXA 2 ) inhibitor 4,5-diphenylimidazole (DPI) in the proliferation of Brucella abortus infection. None of the compounds affected the uptake of Brucella into the macrophages. We determined the effect of neutralizing leukotriene B4 (LTB4) receptor and showed that the uptake of the bacteria was inhibited at 30 min post-infection. M 4 N treatment attenuated intracellular survival of Brucella at 2 h post-incubation but it was not observed in the succeeding time points. DPI treatment showed reduced survival of Brucella at 24 h post-incubation while blocking LTB4 receptor was observed to have a lower intracellular growth at 48 h post-incubation suggesting different action of the inhibitors in the course of the survival of Brucella within the cells. Reduced proliferation of the bacteria in the spleens of mice was observed in animals treated with ZIL or DPI. Increased serum cytokine level of TNF-α and MCP-1 was observed in mice treated with M 4 N or ZIL while a lower IFN-γ level in ZIL-treated mice and a higher IL-12 serum level in DPI-treated mice were observed at 7 d postinfection. At 14 d post-infection, ZIL-treated mice displayed reduced serum level of IL-12 and IL-10. Overall, inhibition of 5-LOX or TXA 2 or a combination therapy promises a potential alternative therapy against B. abortus infection. Furthermore, strong ligands for LTB4 receptor could also be a good candidate for the control of Brucella infection.

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“…5-Lipoxygenase (LO)-deficient mice, which do not produce leukotriene B4 and lipoxin A4, present lower B. abortus loads in spleen and liver with milder liver pathology, as well as increased Th1 responses [ 351 ]. In macrophages, prostaglandin I2 inhibits B. abortus internalisation and attenuates pro- and anti-inflammatory cytokines production [ 352 ], while bacterial loads are decreased in prostaglandin I2-challenged and infected mice [ 352 ]. Altogether, Brucella exploits the eicosanoid pathway to escape the host immune response and survive.…”

Section: Current Knowledge Of Immunosuppression and Chronicity Throug...mentioning

confidence: 99%

Immunosuppressive Mechanisms in Brucellosis in Light of Chronic Bacterial Diseases

2022

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Brucellosis is considered one of the major zoonoses worldwide, constituting a critical livestock and human health concern with a huge socio-economic burden. Brucella genus, its etiologic agent, is composed of intracellular bacteria that have evolved a prodigious ability to elude and shape host immunity to establish chronic infection. Brucella’s intracellular lifestyle and pathogen-associated molecular patterns, such as its specific lipopolysaccharide (LPS), are key factors for hiding and hampering recognition by the immune system. Here, we will review the current knowledge of evading and immunosuppressive mechanisms elicited by Brucella species to persist stealthily in their hosts, such as those triggered by their LPS and cyclic β-1,2-d-glucan or involved in neutrophil and monocyte avoidance, antigen presentation impairment, the modulation of T cell responses and immunometabolism. Attractive strategies exploited by other successful chronic pathogenic bacteria, including Mycobacteria, Salmonella, and Chlamydia, will be also discussed, with a special emphasis on the mechanisms operating in brucellosis, such as granuloma formation, pyroptosis, and manipulation of type I and III IFNs, B cells, innate lymphoid cells, and host lipids. A better understanding of these stratagems is essential to fighting bacterial chronic infections and designing innovative treatments and vaccines.

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Prostaglandin I2 (PGI2) inhibits Brucella abortus internalization in macrophages via PGI2 receptor signaling, and its analogue affects immune response and disease outcome in mice

Cited by 10 publications

References 42 publications

PTGIS May Be a Predictive Marker for Ovarian Cancer by Regulating Fatty Acid Metabolism

PTGIS May Be a Predictive Marker for Ovarian Cancer by Regulating Fatty Acid Metabolism

The In Vitro and In Vivo Effect of Lipoxygenase Pathway Inhibitors Nordihydroguaiaretic Acid and Its Derivative Tetra-O-methyl Nordihydroguaiaretic Acid againstBrucella abortus544

Immunosuppressive Mechanisms in Brucellosis in Light of Chronic Bacterial Diseases

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