Tumor Necrosis Factor Alpha: A Major Cytokine of Brain Neuroinflammation

Muhammad, Mubarak

doi:10.5772/intechopen.85476

Cited by 27 publications

(28 citation statements)

References 51 publications

(38 reference statements)

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“…It is important to highlight that the polymorphisms evaluated in this study affect the expression of their genes or function of the proteins, which act on the fetus’ brain, both in the context of development and inflammatory response [ 34 , 35 , 36 , 37 , 38 , 39 ]. Since the aim of this study was evaluating the role that these polymorphisms could have, in the context of the ZIKV infection, on the fetal brain development, we considered that it would be interesting to evaluate their frequency only in individuals with CZS and individuals who have been exposed in utero to the ZIKV infection but were born normal and, in this sense, the parents were not evaluated, since this analysis would not add information to answer to the aim of the study.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, although these genes and polymorphisms have an important role in neurogenesis or neuroinflammation, they have not been described as capable of causing the phenotypes seen in CZS, such as microcephaly, among others outside the context of the ZIKV infection [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. This could mean that ZIKV infection potentiates the effect of these polymorphisms and, for this reason, they act on individuals’ susceptibility to CZS in the context of ZIKV infection.…”

Section: Discussionmentioning

confidence: 99%

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Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Gomes

Sgarioni

Boquett

et al. 2021

Viruses

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Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Gomes

Sgarioni

Boquett

et al. 2021

Viruses

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“…In this study, we have used the pro-inflammatory cytokine TNF-α as a prominent biomarker to investigate proinflammatory responses (Muhammad, 2019). It is the case however that microglial responses to inflammation involve the complex release and functional interplay of many different cytokines (Lively and Schlichter, 2018).…”

Section: Gas6mentioning

confidence: 99%

Gas6 Inhibits Toll-Like Receptor-Mediated Inflammatory Pathways in Mouse Microglia via Axl and Mer

Gilchrist

Goudarzi

Hafizi

2020

Front. Cell. Neurosci.

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Background: Microglia are well known key regulators of neuroinflammation which feature in multiple neurodegenerative disorders. These cells survey the CNS and, under inflammatory conditions, become "activated" through stimulation of toll-like receptors (TLRs), resulting in changes in morphology and production and release of cytokines. In the present study, we examined the roles of the related TAM receptors, Mer and Axl, and of their ligand, Gas6, in the regulation of microglial pro-inflammatory TNF-α production and microglial morphology. Methods: Primary cultures of murine microglia of wild-type (WT), Mer −/− and Axl −/− backgrounds were stimulated by the TLR4 agonist, lipopolysaccharide (LPS) with or without pre-treatment with Gas6. Gene expression of TNF-α, Mer, and Axl was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) was used to measure TNF-α release from microglia. Immunofluorescence staining of β-actin and the microglial marker Iba1 was performed to reveal microglial morphological changes, with cellular characteristics (area, perimeter, Feret's diameter, minimum Feret, roundness, and aspect ratio) being quantified using ImageJ software. Results: Under basal conditions, TNF-α gene expression was significantly lower in Axl −/− microglia compared to WT cells. However, all microglial cultures robustly responded to LPS stimulation with the upregulation of TNF-α expression to similar degrees. Furthermore, Mer receptor expression was less responsive to LPS stimulation when in Axl knockout cells. The presence of Gas6 consistently inhibited the LPS-induced upregulation of TNF-α in WT, Mer −/− and Axl −/− microglia. Moreover, Gas6 also inhibited LPS-induced changes in the microglial area, perimeter length, and cell roundness in wild-type cells.

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“…This pathological condition is caused by the activation of the neuroimmune cells from the brain astrocytes and microglia. Deregulation of microglia and astrocytes, abnormal pro-inflammatory cytokines (CK) synthesis such as tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), and interferon-γ (IFN-γ), and rise of reactive oxygen and nitrogen species are the most common aspects in neuroinflammation [1][2][3][4]. It has been demonstrated that neuroinflammation plays a pivotal role in many neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, Huntington disease, spinocerebellar ataxia, and multiple sclerosis [5,6].…”

Section: Introductionmentioning

confidence: 99%

Adenosine Receptors as Neuroinflammation Modulators: Role of A1 Agonists and A2A Antagonists

Navia

Ben

Lambertucci

et al. 2020

Cells

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The pathological condition of neuroinflammation is caused by the activation of the neuroimmune cells astrocytes and microglia. The autacoid adenosine seems to be an important neuromodulator in this condition. Its main receptors involved in the neuroinflammation modulation are A1AR and A2AAR. Evidence suggests that A1AR activation produces a neuroprotective effect and A2AARs block prevents neuroinflammation. The aim of this work is to elucidate the effects of these receptors in neuroinflammation using the partial agonist 2′-dCCPA (2-chloro-N6-cyclopentyl-2′-deoxyadenosine) (C1 KiA1AR = 550 nM, KiA2AAR = 24,800 nM, and KiA3AR = 5560 nM, α = 0.70, EC50A1AR = 832 nM) and the newly synthesized in house compound 8-chloro-9-ethyl-2-phenethoxyadenine (C2 KiA2AAR = 0.75 nM; KiA1AR = 17 nM and KiA3AR = 227 nM, IC50A2AAR = 251 nM unpublished results). The experiments were performed in in vitro and in in vivo models of neuroinflammation. Results showed that C1 was able to prevent the inflammatory effect induced by cytokine cocktail (TNF-α, IL-1β, and IFN-γ) while C2 possess both anti-inflammatory and antioxidant properties, counteracting both neuroinflammation in mixed glial cells and in an animal model of neuroinflammation. In conclusion, C2 is a potential candidate for neuroinflammation therapy.

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Tumor Necrosis Factor Alpha: A Major Cytokine of Brain Neuroinflammation

Cited by 27 publications

References 51 publications

Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Gas6 Inhibits Toll-Like Receptor-Mediated Inflammatory Pathways in Mouse Microglia via Axl and Mer

Adenosine Receptors as Neuroinflammation Modulators: Role of A1 Agonists and A2A Antagonists

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