Effect of malaria components on blood mononuclear cells involved in immune response

Punsawad, Chuchard

doi:10.1016/s2221-1691(13)60151-3

Cited by 14 publications

(15 citation statements)

References 48 publications

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“…Accumulating evidence suggests that the protective (antiinflammatory) role of Hsp70 is mediated through downregulation of NF-κB, since NF-κB activation and translocation into the nucleus promotes elevated proinflammatory mediators (14,(16)(17)(18)(19)(20)(21)41,50,72,73). Consistent with this notion, we and others have demonstrated that overexpression of Hsp70 protein blocks nuclear translocation of NF-κB and thereby reduces proinflammatory mediator production (19)(20)(21)50).…”

Section: Discussionsupporting

confidence: 75%

“…induce the production of inflammatory mediators through NF-κB activation (16). Results presented here show that PfHz induces rapid translocation of NF-κB into the nucleus with peak levels by 8 h. In addition, after induction of Hsp70 with elevated temperature (42°C), PfHz remained capable of causing NF-κB activation, although to a lesser extent due to enhanced Hsp70 expression.…”

Section: Discussionmentioning

confidence: 59%

“…Additional studies from our group and others have shown that cultured peripheral blood mononuclear cells (PBMCs) treated with physiological concentrations of PfHz have the ability to alter cytokines, chemokines and effector molecules that mimic observations during human falciparum infections (6, [14][15][16]. Although the signaling pathways for PfHz require further characterization, nuclear factor-kappa B (NF-κB) appears to be a pivotal transcription factor in a number of inflammatory diseases, since it is a critical upstream regulator of gene expression due to the presence of consensus sequences in the promoter region of inflammatory mediators (16)(17)(18). In unstimulated conditions, NF-κB remains bound to its inhibitor, kappa B (IκB), in the cytoplasm as an inactive form (16)(17)(18).…”

Section: Inflammatory Mediator and Glutamine Measurementsmentioning

confidence: 99%

“…Although the signaling pathways for PfHz require further characterization, nuclear factor-kappa B (NF-κB) appears to be a pivotal transcription factor in a number of inflammatory diseases, since it is a critical upstream regulator of gene expression due to the presence of consensus sequences in the promoter region of inflammatory mediators (16)(17)(18). In unstimulated conditions, NF-κB remains bound to its inhibitor, kappa B (IκB), in the cytoplasm as an inactive form (16)(17)(18). Following stimulation of cells, IκB is phosphorylated by IκB kinase to rapidly degrade and activate the NF-κB dimer for translocation into the nucleus, where it binds to the enhancer regions on the promoter of target genes (16)(17)(18).…”

Section: Inflammatory Mediator and Glutamine Measurementsmentioning

confidence: 99%

“…In unstimulated conditions, NF-κB remains bound to its inhibitor, kappa B (IκB), in the cytoplasm as an inactive form (16)(17)(18). Following stimulation of cells, IκB is phosphorylated by IκB kinase to rapidly degrade and activate the NF-κB dimer for translocation into the nucleus, where it binds to the enhancer regions on the promoter of target genes (16)(17)(18).…”

Section: Inflammatory Mediator and Glutamine Measurementsmentioning

confidence: 99%

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Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

Kempaiah

Dokładny

Karim

et al. 2016

Mol Med

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Severe malarial anemia (SMA; hemoglobin [Hb] <5.0 g/dL) is a leading global cause of morbidity and mortality among children residing in Plasmodium falciparum transmission regions. Exploration of molecular pathways through global gene expression profiling revealed that SMA was characterized by decreased HSPA1A, a heat shock protein 70 (Hsp70) coding gene. Hsp70 is a ubiquitous chaperone that regulates nuclear factor-kappa B (NF-κB) signaling and production of proinflammatory cytokines known to be important in malaria pathogenesis (for example, IL-1β, IL-6 and TNF-α). Since the role of host Hsp70 in malaria pathogenesis is unexplored, we investigated Hsp70 and molecular pathways in children with SMA. Validation experiments revealed that leukocytic HSP70 transcripts were reduced in SMA relative to nonsevere malaria, and that intraleukocytic hemozoin (PfHz) was associated with lower HSP70. HSP70 was correlated with reticulocyte production and Hb. Since glutamine (Gln) upregulates Hsp70, modulates NF-κB activation and attenuates overexpression of proinflammatory cytokines, circulating Gln was measured in children with malaria. Reduced Gln was associated with increased risk of developing SMA. Treatment of cultured peripheral blood mononuclear cells (PBMCs) with PfHz caused a time-dependent decrease in Hsp70 transcripts/protein and NF-κB activation. Gln treatment of PBMCs overcame PfHz-induced suppression of HSP70 transcripts/protein, reduced NF-κB activation and suppressed overexpression of IL-1β, IL-6 and TNF-α. These findings demonstrate that SMA is characterized by reduced intraleukocytic HSP70 and circulating Gln, and that PfHz-induced suppression of HSP70 can be reversed by Gln. Thus, Gln supplementation may offer important immunotherapeutic options for futures studies in children with SMA.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 59%

Section: Inflammatory Mediator and Glutamine Measurementsmentioning

confidence: 99%

Section: Inflammatory Mediator and Glutamine Measurementsmentioning

confidence: 99%

Section: Inflammatory Mediator and Glutamine Measurementsmentioning

confidence: 99%

See 3 more Smart Citations

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

Kempaiah

Dokładny

Karim

et al. 2016

Mol Med

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TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review

Mukherjee

Karmakar

Babu

2016

The Brazilian Journal of Infectious Diseases

309

251

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During the course of evolution, multicellular organisms have been orchestrated with an efficient and versatile immune system to counteract diverse group of pathogenic organisms. Pathogen recognition is considered as the most critical step behind eliciting adequate immune response during an infection. Hitherto Toll-like receptors (TLRs), especially the surface ones viz. TLR2 and TLR4 have gained immense importance due to their extreme ability of identifying distinct molecular patterns from invading pathogens. These pattern recognition receptors (PRRs) not only act as innate sensor but also shape and bridge innate and adaptive immune responses. In addition, they also play a pivotal role in regulating the balance between Th1 and Th2 type of response essential for the survivability of the host. In this work, major achievements rather findings made on the typical signalling and immunopathological attributes of TLR2 and TLR4 mediated host response against the major infectious diseases have been reviewed. Infectious diseases like tuberculosis, trypanosomiasis, malaria, and filariasis are still posing myriad threat to mankind. Furthermore, increasing resistance of the causative organisms against available therapeutics is also an emerging problem. Thus, stimulation of host immune response with TLR2 and TLR4 agonist can be the option of choice to treat such diseases in future.

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Antiplasmodial and interferon-gamma-modulating activities of the aqueous extract of stone breaker (Phyllanthus niruri Linn.) in malaria infection

Jeje

Bando

Azad

et al. 2023

Parasitology International

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Effect of malaria components on blood mononuclear cells involved in immune response

Cited by 14 publications

References 48 publications

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review

Antiplasmodial and interferon-gamma-modulating activities of the aqueous extract of stone breaker (Phyllanthus niruri Linn.) in malaria infection

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