The role of nuclear factor kappa B (NF-κB) in filarial pathology

Fordjour, Fatima Amponsah; Asiedu, Ebenezer; Larbi, Amma; Kwarteng, Alexander

doi:10.1007/s12079-021-00607-5

Cited by 6 publications

(6 citation statements)

References 69 publications

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“…Downregulation and impaired activation of NF-κB-p65 and NF-κB-p50/105 in mouse macrophages during the course of infection contributes to macrophage polarization towards M 2 and M reg phenotypes and downregulation of proinflammatory IL-12 release and increased secretion of Th 2 /Th reg cytokines: IL-4 and IL-10, respectively [ 126 ]. IL-10 and IL-12 release is also impaired in human DCs exposed to B. malayi microfilariae [ 130 ]; however, pathologies during infection are associated with increased Th 1 /Th 17 responses [ 131 ] and enhanced angiogenesis [ 132 ]. NF-κB is involved in both angiogenesis [ 133 ] and inflammation [ 134 ] regulation.…”

Section: Helminthsmentioning

confidence: 99%

The Role of Nuclear Factor Kappa B (NF-κB) in the Immune Response against Parasites

Bąska

Norbury

2022

Pathogens

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The immune system consists of various cells, organs, and processes that interact in a sophisticated manner to defend against pathogens. Upon initial exposure to an invader, nonspecific mechanisms are raised through the activation of macrophages, monocytes, basophils, mast cells, eosinophils, innate lymphoid cells, or natural killer cells. During the course of an infection, more specific responses develop (adaptive immune responses) whose hallmarks include the expansion of B and T cells that specifically recognize foreign antigens. Cell to cell communication takes place through physical interactions as well as through the release of mediators (cytokines, chemokines) that modify cell activity and control and regulate the immune response. One regulator of cell states is the transcription factor Nuclear Factor kappa B (NF-κB) which mediates responses to various stimuli and is involved in a variety of processes (cell cycle, development, apoptosis, carcinogenesis, innate and adaptive immune responses). It consists of two protein classes with NF-κB1 (p105/50) and NF-κB2 (p100/52) belonging to class I, and RelA (p65), RelB and c-Rel belonging to class II. The active transcription factor consists of a dimer, usually comprised of both class I and class II proteins conjugated to Inhibitor of κB (IκB). Through various stimuli, IκB is phosphorylated and detached, allowing dimer migration to the nucleus and binding of DNA. NF-κB is crucial in regulating the immune response and maintaining a balance between suppression, effective response, and immunopathologies. Parasites are a diverse group of organisms comprised of three major groups: protozoa, helminths, and ectoparasites. Each group induces distinct effector immune mechanisms and is susceptible to different types of immune responses (Th1, Th2, Th17). This review describes the role of NF-κB and its activity during parasite infections and its contribution to inducing protective responses or immunopathologies.

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Section: Helminthsmentioning

confidence: 99%

The Role of Nuclear Factor Kappa B (NF-κB) in the Immune Response against Parasites

Bąska

Norbury

2022

Pathogens

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“…9 The pathology is known to progress due to elevated inflammatory processes that unfolds in the presence of filarial antigen. [10][11][12] Data from field trials have shown potency of some antibiotics (doxycycline and minocycline) against LF. 7,[13][14][15][16] This notwithstanding, these antibiotics have a longer regimen duration and do not support national treatment programs.…”

Section: Introductionmentioning

confidence: 99%

“…DEC has also been reported to cause severe side effects such as fever, gastrointestinal disturbance, headache, malaise, and skin rash that reduce patient's compliance 9 . The pathology is known to progress due to elevated inflammatory processes that unfolds in the presence of filarial antigen 10–12 …”

Section: Introductionmentioning

confidence: 99%

Use of medicinal plants as a remedy against lymphatic filariasis: Current status and future prospect

Fordjour,

Osei‐Poku,

Genfi

et al. 2023

Health Science Reports

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Despite the successes achieved so far with the Global Programme to Eliminate Lymphatic Filariasis, there is still an appreciable number of lymphatic filarial patients who need alternative treatment and morbidity management strategies.The unresponsiveness of some cohorts to the drugs used in the mass drug administration program is currently raising a lot of questions and this needs urgent attention. Natural medicinal plants have a long-standing history of being effective against most disease conditions. Countries such as India have been able to integrate their natural plant remedies into the treatment of lymphatic filarial conditions, and the results are overwhelmingly positive. Components of Azadirachta indica A. Juss, Parkia biglobosa, Adansonia digitata, and Ocimum spp have been shown to have anti-inflammatory, anticancerous, and antimicrobial activities in animal models. Therefore, this review calls for attention toward the use of natural plant components as an alternate treatment against lymphatic filariasis to help reduce the World Health Organization's burden of providing drugs for people in need of treatment every year.

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“…As a dominant NF-κB/IκBα signaling pathways are essential for resistance to heat stress-induced ROS production in pulmonary microvascular endothelial cells regulatory kinase in the classic NF-κB signaling pathway, IκBα serves a prominent role in apoptosis (17). In addition, the IκBα/NF-κB signaling pathway is one of the most popular antitumor targets (18). The results of the present study revealed a novel mechanism for HS-induced NF-κB activation in rat pulmonary microvascular endothelial cells (PMVECs) without IκBα degradation, which differs from the classic NF-κB signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells

et al. 2021

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The results of a previous study demonstrated that heat stress (HS) triggered oxidative stress, which in turn induced the apoptosis of epithelial cells. These results uncovered a novel mechanism underlying the activation of NF-κB in primary human umbilical vein endothelial cells. The present study aimed to further investigate the role of NF-κB/IκBα signaling pathways in the inhibition of HS-induced reactive oxygen species (ROS) generation and cytotoxicity in endothelial cells. The results of the present study demonstrated that HS triggered a significant amount of NF-κB and IκBα nuclear translocation without IκBα degradation in a time-dependent manner. Mutant constructs of IκBα phosphorylation sites (Ser32, Ser36) were employed in rat pulmonary microvascular endothelial cells (PMVECs). Cell Counting Kit-8 assays demonstrated that both the small interfering (si)RNA-mediated knockdown of p65 and IκBα mutant constructs significantly decreased cell viability and aggravated ROS accumulation in HS-induced rat PMVECs compared with the control. Additionally, western blot analysis revealed that p65 siRNA attenuated the protein expression of IκBα. However, IκBα mutant constructs failed to attenuate NF-κB activation and nuclear translocation, indicating that IκBα-independent pathways contributed to NF-κB activity and nucleus translocation in a time-dependent manner following HS. Collectively, the results of the present study suggested that the NF-κB/IκBα pathway was essential for resistance to HS-induced ROS production and cytotoxicity in rat PMVECs, and that it could be a potential therapeutic target to reduce the mortality and morbidity of heat stroke.

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The role of nuclear factor kappa B (NF-κB) in filarial pathology

Cited by 6 publications

References 69 publications

The Role of Nuclear Factor Kappa B (NF-κB) in the Immune Response against Parasites

The Role of Nuclear Factor Kappa B (NF-κB) in the Immune Response against Parasites

Use of medicinal plants as a remedy against lymphatic filariasis: Current status and future prospect

NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells

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