Abstract
BackgroundMalaria parasites and their products can activate a specific immune response by stimulating cytokine production in the host’s immune cells. Transcription nuclear factor kappa B (NF-κB) is an important regulator for the control of many pro-inflammatory genes, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF). The activation and expression of NF-κB p65 in peripheral blood mononuclear cells (PBMCs) of malaria patients were investigated and correlated with the levels of IL-10 and TNF to study the nature of NF-κB p65 and its linkage to inflammatory cytokines.MethodsThe sample group comprised 33 patients admitted with malaria caused by Plasmodium vivax (n = 11), uncomplicated Plasmodium falciparum (n = 11), and complicated Plasmodium falciparum (n = 11). Peripheral blood was collected at admission and on day 7 for PBMC isolation. Healthy subjects were used as a control group. The expressions of NF-κB p65 in the PBMCs from malaria patients and the plasma levels of IL-10 and TNF were measured by using enzyme-linked immunosorbent assay (ELISA). The immunofluorescence technique was used to determine NF-κB nuclear translocation.ResultsAt admission, patients with P. vivax and uncomplicated P. falciparum had significantly elevated phospho-NF-κB p65 levels in the PBMCs compared with those of healthy controls. However, patients with complicated P. falciparum malaria had decreased levels of phospho-NF-κB p65. On day 7 post-treatment, significantly increased phospho-NF-κB p65 was found in the PBMCs of patients with complicated P. falciparum, compared with healthy controls. The plasma level of IL-10 was elevated in day 0 in patients with complicated P. falciparum malaria and was found to be negatively correlated with phospho-NF-κB p65 level (rs = −0.630, p = 0.038). However, there was no correlation between phospho-NF-κB p65 expression and TNF level in patients with complicated P. falciparum malaria.ConclusionsThis is the first report demonstrating alterations in NF-κB p65 activity in the PBMCs of malaria patients. The altered lower features of NF-κB p65 in the PBMCs of patients with complicated P. falciparum at admission could be due to a suppressive effect of high IL-10 associated with complicated P. falciparum malaria.
Highlights
Malaria parasites and their products can activate a specific immune response by stimulating cytokine production in the host’s immune cells
Patients diagnosed with P. vivax malaria were administered chloroquine and primaquine, whereas patients with P. falciparum malaria were treated with artesunate and mefloquine
Phospho-NF-κB p65 levels were significantly elevated in the peripheral blood mononuclear cells (PBMCs) of patients with P. vivax (0.182 ± 0.04, p < 0.001) and uncomplicated P. falciparum malaria (0.250 ± 0.10, p < 0.001), compared to the healthy controls (0.104 ± 0.04)
Summary
Malaria parasites and their products can activate a specific immune response by stimulating cytokine production in the host’s immune cells. Transcription nuclear factor kappa B (NF-κB) is an important regulator for the control of many pro-inflammatory genes, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF). Nuclear factor kappa B (NF-κB) plays a crucial role in immune and inflammatory responses, through the regulation of various genes involved in pro-inflammatory cytokines, adhesion molecules, chemokines, inducible enzymes, and apoptosis [1]. Mammals express five NFκB protein members: NF-κB-1 (p50), NF-κB-2 (p52), Rel A (p65), Rel B, and c-Rel [2]. These proteins have a structurally conserved amino-terminal (300 amino-acid) region, containing dimerization, nuclear localization and DNA binding domains. Activated NF-κB translocates into the nucleus, where it binds to the DNA regulatory site to regulate specific gene expressions [2,3]
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