Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria

Krücken, Jürgen; Delić, Denis; Pauen, Heike; Wojtalla, Anna; El‐Khadragy, Manal F.; Dkhil, Mohamed A.; Mossmann, Horst; Wunderlich, Frank

doi:10.1186/1475-2875-8-54

Cited by 42 publications

(106 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A significant elevation in serum TNF-α was detected in LPS and drugtreated animals (Figure 4). It was found that the sole administration of AQ (25,50, and 100 mg/kg, oral) and/or CQ (25, 50, and 100 mg/kg, oral) caused no significant changes in liver glutathione content, lipid peroxidation, and protein carbonylation (Table 1). When animals were pre-treated with LPS (100 µg/kg, i.p), significant increase in lipid peroxidation and protein carbonylation, along with liver tissue glutathione depletion were detected after AQ (25,50, and 100 mg/kg, oral) and/or CQ (25,50, and 100 mg/kg, oral) administration (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…It was found that AQ (25,50, and 100 mg/kg, oral) caused no significant changes in serum level of liver injury biomarkers when it was administered alone (Figure 1). CQ administration (25,50, and 100 mg/kg, oral) also caused no significant elevation in ALT, LDH, AST, and serum total bilirubin as compared to control animals ( Figure 2). Rats were pre-treated with a non-injurious dose of bacterial endotoxin (100 µg/kg of LPS, i.p).…”

Section: Resultsmentioning

confidence: 99%

“…Rats were pre-treated with a non-injurious dose of bacterial endotoxin (100 µg/kg of LPS, i.p). Then, animals received AQ (25,50, and 100 mg/kg, oral) and/or CQ (25, 50, and 100 mg/kg, oral) ( Figure 1). Interestingly, it was found that AQ and CQ caused a significant and severe elevation in serum ALT, LDH, and AST level when these drugs were administered to LPS-treated animals (Figure 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

“…[22][23][24] On the other side, malaria infection is associated with an inflammatory response in many tissues including liver. [25][26][27] Immune cells are aggregated in the liver of malaria-infected patients. [25][26][27] This might interact with malaria drug therapy and finally, leads to drug-induced liver injury.…”

Section: Introductionmentioning

confidence: 99%

“…[25][26][27] Immune cells are aggregated in the liver of malaria-infected patients. [25][26][27] This might interact with malaria drug therapy and finally, leads to drug-induced liver injury. The current investigation was designed to evaluate if a modest inflammation interacts with nonhepatotoxic doses of antimalarial drugs to induce liver injury in rats.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Concurrent Inflammation Augments Antimalarial Drugs-Induced Liver Injury in Rats

et al. 2016

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Concurrent Inflammation Augments Antimalarial Drugs-Induced Liver Injury in Rats

et al. 2016

View full text Add to dashboard Cite

Hepatic miRNA expression reprogrammed by Plasmodium chabaudi malaria

et al. 2010

Self Cite

View full text Add to dashboard Cite

Evidence is accumulating that miRNAs are critically implicated in the outcome of diseases, but little information is available for infectious diseases. This study investigates the hepatic miRNA signature in female C57BL/6 mice infected with self-healing Plasmodium chabaudi malaria. Primary infections result in approximately 50% peak parasitemia on day 8 p.i., approximately 80% survival, and development of protective immunity. The latter is evidenced as 100% survival and 1.5% peak parasitemia upon homolog re-infections of those mice which are still alive on day 56 after primary infection. Such immune mice exhibit increased levels of IgG2a and IgG2b isotypes and still contain P. chabaudi-infected erythrocytes in their livers as revealed by light microscopy and PCR analysis. Primary infections, but not secondary infections, induce an upregulation of hepatic mRNAs encoding IL-1β, TNFα, IFNγ, NF-κB, and iNOS, and a downregulation of mRNAs for CYP7A1 and SULT2A2, respectively. Using miRXplore microarrays containing 634 mouse miRNAs in combination with quantitative RT-PCR, the liver is found to respond to primary infections with an upregulation of the three miRNA species miR-26b, MCMV-miR-M23-1-5p, and miR-1274a, and a downregulation of the 16 miRNA species miR-101b, let-7a, let-7g, miR-193a-3p, miR-192, miR-142-5p, miR-465d, miR-677, miR-98, miR-694, miR-374(*), miR-450b-5p, miR-464, miR-377, miR-20a(*), and miR-466d-3p, respectively. Surprisingly, about the same pattern of miRNA expression is revealed in immune mice, and this pattern is even sustained upon homolog re-infections of immune mice. These data suggest that development of protective immunity against malarial blood stages of P. chabaudi is associated with a reprogramming of the expression of distinct miRNA species in the female mouse liver.

show abstract

Organ-specific testosterone-insensitive response of miRNA expression of C57BL/6 mice to Plasmodium chabaudi malaria

et al. 2012

View full text Add to dashboard Cite

Increasing evidence critically implicates miRNAs in the pathogenesis of diseases, but little is known in context with infectious diseases. This study investigates as to whether the testosterone-induced persistent susceptibility to blood-stage malaria of Plasmodium chabaudi coincides with changes in miRNA expression of the anti-malaria effectors sites spleen and liver. Female C57BL/6 mice were treated with vehicle or testosterone (T) for 3 weeks. Then, T treatment was discontinued for 12 weeks before challenge with 10(6) P. chabaudi-parasitized erythrocytes. The miRNA expression was examined after 12 weeks of T withdrawal and during infections at peak parasitemia on day 8 p.i. using miRXplore™ microarray technology. P. chabaudi infections induce an organ-specific response of miRNA expression. We can identify 25 miRNA species to be downregulated by more than 2-fold in the spleen and 169 miRNA species in the liver. Among these 194 miRNA species, there are 12 common miRNA species that are downregulated by 0.48-0.14-fold in both spleen and liver, which are miR-194, miR-192, miR-193A-3P, miR-145, miR-16, miR-99A, miR-99B, miR-15A, miR-152, let-7G, let-7B, and miR-455-3P. Only in the liver, there is an upregulation of the miR-142-5p by 2.5-fold and miR-342-3p by 5.1-fold. After 12 weeks of T withdrawal, the spleen exhibits only the miR-200A that is upregulated by 2.7-fold. In the liver, miR-376B, miR-493*, and miR-188-3P are upregulated by 2.4-fold, 2.2-fold, and 2.1-fold, respectively, and miR-347, miR-200A, and miR-200B are downregulated by approximately 0.4-fold. Upon infection, however, these changes are not sustained, i.e., the miRNA expressions of both spleen and liver of T-pretreated mice exhibit the same response to P. chabaudi malaria as that of vehicle-treated control mice. Our data suggest (1) that the P. chabaudi-induced downregulation of miRNA expression in spleen and liver is required to allow the upregulation of their numerous target genes in response to infection, and (2) that the T-induced persistent susceptibility to P. chabaudi does not affect the responsiveness of miRNA expression in spleen and liver to blood-stage malaria.

show abstract

Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria

Cited by 42 publications

References 51 publications

Concurrent Inflammation Augments Antimalarial Drugs-Induced Liver Injury in Rats

Concurrent Inflammation Augments Antimalarial Drugs-Induced Liver Injury in Rats

Hepatic miRNA expression reprogrammed by Plasmodium chabaudi malaria

Organ-specific testosterone-insensitive response of miRNA expression of C57BL/6 mice to Plasmodium chabaudi malaria

Contact Info

Product

Resources

About