scholarly journals Deletion of the transcriptional regulator GntR affects apoptosis and autophagy in Brucella abortus-infected RAW 264.7 cells

2020 ◽  
Author(s):  
Zhiqiang Li ◽  
Shujuan Wei ◽  
Shuli Wang ◽  
Li Xi ◽  
Yanyan Cui ◽  
...  

Abstract Background: Brucellosis is an important zoonotic disease caused by the pathogen Brucella. Regulating apoptosis and autophagy is the prerequisite for the intracellular survival of Brucella. GntR is an important transcriptional regulator of Brucella that can regulate the expression of many target genes, and then play a regulatory role in many cell processes, including regulation apoptosis and autophagy. Therefore, understanding the relationship between GntR and apoptosis and autophagy is crucial to comprehending the pathogenic mechanism of Brucella. Methods: In the present study, we described the influence of GntR on apoptosis and autophagy after the infection of RAW 264.7 cells with Brucella. We constructed the GntR mutant strain (2308ΔGntR) of Brucella abortus 2308 (S2308). Following the infection of the RAW 264.7 cells with S2308 and 2308ΔGntR, apoptosis and autophagy were detected. Results: Western blot analysis and flow cytometry analysis indicated that the apoptosis rate of the 2308ΔGntR-infected group was remarkably higher than that of the S2308-infected group. Confocal laser microscopy experiments indicated the presence of the P62 protein as punctate aggregates in the 2308ΔGntR group. Conclusion: These results showed that 2308ΔGntR promoted apoptosis and inhibited autophagy in the RAW 264.7 cells during Brucella infection.

2018 ◽  
Vol 28 (10) ◽  
pp. 1723-1729 ◽  
Author(s):  
Tran Xuan Ngoc Huy ◽  
Alisha Wehdnesday Bernardo Reyes ◽  
Huynh Tan Hop ◽  
Lauren Togonon Arayan ◽  
Vu Hai Son ◽  
...  

2008 ◽  
Vol 28 (8) ◽  
pp. 2626-2636 ◽  
Author(s):  
Inés Pineda Torra ◽  
Naima Ismaili ◽  
Jonathan E. Feig ◽  
Chong-Feng Xu ◽  
Claudio Cavasotto ◽  
...  

ABSTRACT Dysregulation of liver X receptor α (LXRα) activity has been linked to cardiovascular and metabolic diseases. Here, we show that LXRα target gene selectivity is achieved by modulation of LXRα phosphorylation. Under basal conditions, LXRα is phosphorylated at S198; phosphorylation is enhanced by LXR ligands and reduced both by casein kinase 2 (CK2) inhibitors and by activation of its heterodimeric partner RXR with 9-cis-retinoic acid (9cRA). Expression of some (AIM and LPL), but not other (ABCA1 or SREBPc1) established LXR target genes is increased in RAW 264.7 cells expressing the LXRα S198A phosphorylation-deficient mutant compared to those with WT receptors. Surprisingly, a gene normally not expressed in macrophages, the chemokine CCL24, is activated specifically in cells expressing LXRα S198A. Furthermore, inhibition of S198 phosphorylation by 9cRA or by a CK2 inhibitor similarly promotes CCL24 expression, thereby phenocopying the S198A mutation. Thus, our findings reveal a previously unrecognized role for phosphorylation in restricting the repertoire of LXRα-responsive genes.


2017 ◽  
Vol 27 (3) ◽  
pp. 616-623 ◽  
Author(s):  
Tran Xuan Ngoc Huy ◽  
Alisha Wehdnesday Bernardo Reyes ◽  
Huynh Tan Hop ◽  
Lauren Togonon Arayan ◽  
WonGi Min ◽  
...  

2012 ◽  
Vol 158 (3-4) ◽  
pp. 322-328 ◽  
Author(s):  
Dong Hyeok Kim ◽  
Jeong Ju Lim ◽  
Jin Ju Lee ◽  
Dae Geun Kim ◽  
Hu Jang Lee ◽  
...  

2020 ◽  
Vol 242 ◽  
pp. 108586
Author(s):  
Alisha Wehdnesday Bernardo Reyes ◽  
Son Hai Vu ◽  
Tran Xuan Ngoc Huy ◽  
WonGi Min ◽  
Hu Jang Lee ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiena Wu ◽  
Ruiyin Guo ◽  
Jinwei Chai ◽  
Weichen Xiong ◽  
Maolin Tian ◽  
...  

Acne vulgaris is a common adolescent skin condition which is mainly caused by Propionibacterium acnes overcolonization and subsequent inflammation. Our previous studies have demonstrated that Cath-MH, an antimicrobial peptide from the skin of the frog Microhyla heymonsivogt, possesses potential antimicrobial, LPS-binding, and anti-septicemic properties. However, its protective effects and potential mechanisms against acne vulgaris are still unclear. In the present study, its anti-P. acnes effects were measured by two-fold broth dilution method, agglutination assay, scanning electron microscopy and confocal laser scanning microscopy experiments. Its treatment potential for acne vulgaris was further evaluated in mice ear inoculated by P. acnes. In addition, the binding ability between Cath-MH and LTA was measured by the Circular Dichroism and antibacterial assay. Moreover, the anti-inflammatory efficiency of Cath-MH was evaluated in LTA- and LPS-induced RAW 264.7 macrophage cells. Cath-MH was found to kill P. acnes with a MIC value of about 1.56 μM by membrane disruption mechanism. It also exhibited agglutination activity against P. acnes. Cath-MH was able to bind LTA as well as LPS, inhibit LTA/LPS-stimulated TLR2/4 expression, and subsequently decreased the inflammatory response in RAW 264.7 cells. As expected, Cath-MH alleviated the formation of edema and the infiltration of inflammatory cells in acne mouse model with concurrent suppression of P. acnes growth and inflammatory cytokines expression in vivo. The potent P. acnes inhibition activity combined with powerful anti-inflammatory effect of Cath-MH indicates its potential as a novel therapeutic option for acne vulgaris.


2021 ◽  
Vol 7 ◽  
Author(s):  
Tran Xuan Ngoc Huy ◽  
Trang Thi Nguyen ◽  
Alisha Wehdnesday Bernardo Reyes ◽  
Son Hai Vu ◽  
WonGi Min ◽  
...  

Protective efficiency of a combination of four recombinant Brucella abortus (B. abortus) proteins, namely outer membrane protein (Omp) 16, Omp19, Omp28, and 50S ribosomal protein L7/L12 was evaluated as a combined subunit vaccine (CSV) against B. abortus infection in RAW 264.7 cell line and murine model. The immunoreactivity of these four recombinant proteins as well as pCold-TF vector reacted with Brucella-positive serum individually, but not with Brucella-negative serum by immunoblotting assay. CSV-treated RAW 264.7 cells significantly induced production of IFN-γ and IL-12 while decreased IL-10 production at the late stage of infection compared to PBS-treated control cells. In addition, the enhancement of nitric oxide production together with cytokines secretion profile in CSV-treated cells proved that CSV notably activated bactericidal mechanisms in macrophages. Consistently, mice immunized with CSV strongly elicited production of pro-inflammatory cytokines TNF-α, IL-6 and MCP-1 compared to PBS control group. Moreover, the concentration of IFN-γ was >IL-10 and titers of IgG2a were also heightened compared to IgG1 in CSV-immunized mice which suggest that CSV induced predominantly T helper 1 T cell. These results suggest that the CSV used in the present study is a potential candidate as a preventive therapy against brucellosis.


2015 ◽  
Vol 362 (11) ◽  
Author(s):  
Lauren Togonon Arayan ◽  
Hannah Leah Simborio ◽  
Alisha Wehdnesday Bernardo Reyes ◽  
Huynh Tan Hop ◽  
WonGi Min ◽  
...  

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