MiR-155: An Important Regulator of Neuroinflammation

Zingale, Valeria Domenica; Gugliandolo, Agnese; Mazzon, Emanuela

doi:10.3390/ijms23010090

Cited by 84 publications

(56 citation statements)

References 129 publications

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“…Among the different miRNA, miRNA155 is highly expressed in numerous tissues, including the brain, suggesting its pro-inflammatory action in CNS. miRNA155 induces neuroinflammation through a reduction in the endogenous anti-inflammatory response resulting in increased inflammation [ 54 ]. Neuroinflammation has been identified as a causative factor of multiple neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

et al. 2022

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Alcoholism is one of the most common diseases that can lead to the development of several chronic diseases including steatosis, and cognitive dysfunction. Statins are lipid-lowering drugs that are commonly prescribed for patients with fatty liver diseases; however, the exact effect of statins on cognitive function is still not fully understood. In the present study, we have investigated the molecular and microscopic basis of cognitive impairment induced by alcohol and/or Atorvastatin (ATOR) administration to male Wistar albino rats and explored the possible protective effect of acetylsalicylic acid (ASA). The biochemical analysis indicated that either alcohol or ATOR or together in combination produced a significant increase in the nucleotide-binding domain–like receptor 3 (NLRP3), interleukin-1β (IL-1β) miRNA155 expression levels in the frontal cortex of the brain tissue. The histological and morphometric analysis showed signs of degeneration in the neurons and the glial cells with aggregations of inflammatory cells and a decrease in the mean thickness of the frontal cortex. Immunohistochemical analysis showed a significant increase in the caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex. Interestingly, administration of ASA reversed the deleterious effect of the alcohol and ATOR intake and improved the cognitive function as indicated by biochemical and histological analysis. ASA significantly decreased the expression levels of miRNA155, NLRP3, and IL1B, and produced a significant decrease in caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex with a reduction in the process of neuroinflammation and neuronal damage. To further investigate these findings, we have performed an extensive molecular docking study to investigate the binding affinity of ASA to the binding pockets of the NLRP3 protein. Our results indicated that ASA has high binding scores toward the active sites of the NLRP3 NACHT domain with the ability to bind to the NLRP3 pockets by a set of hydrophilic and hydrophobic interactions. Taken together, the present study highlights the protective pharmacological effect of ASA to attenuate the deleterious effect of alcohol intake and long term ATOR therapy on the cognitive function via targeting miRNA155 and NLRP3 proteins.

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Section: Discussionmentioning

confidence: 99%

Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

et al. 2022

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“…MiR-155-5p plays a multifunctional role in innate and adaptive immunity and inflammation, so that its aberrant overexpression represents a potential disease biomarker or therapeutic target in states of chronic inflammation [ 109 ]. Its involvement in neuroinflammation, vascular dysfunction and neurodegeneration has been documented in animal and human studies [ 110 , 111 ]. Interestingly, a miR-155-5p target, i.e., NRG3 (neuregulin-3), is a ligand of ERBB4, and is thought to regulate neuroblast proliferation, migration and differentiation; repair after nerve injury; synapse formation; regulation of glutamate; GABA and dopamine release [ 112 ].…”

Section: Discussionmentioning

confidence: 99%

Expression and Biological Functions of miRNAs in Chronic Pain: A Review on Human Studies

Sabina

Panìco

Mincarone

et al. 2022

IJMS

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Chronic pain is a major public health problem and an economic burden worldwide. However, its underlying pathological mechanisms remain unclear. MicroRNAs (miRNAs) are a class of small noncoding RNAs that post-transcriptionally regulate gene expression and serve key roles in physiological and pathological processes. This review aims to synthesize the human studies examining miRNA expression in the pathogenesis of chronic primary pain and chronic secondary pain. Additionally, to understand the potential pathophysiological impact of miRNAs in these conditions, an in silico analysis was performed to reveal the target genes and pathways involved in primary and secondary pain and their differential regulation in the different types of chronic pain. The findings, methodological issues and challenges of miRNA research in the pathophysiology of chronic pain are discussed. The available evidence suggests the potential role of miRNA in disease pathogenesis and possibly the pain process, eventually enabling this role to be exploited for pain monitoring and management.

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“…It is an important regulator of neuroinflammation in diverse pathological conditions e.g. multiple sclerosis and Alzheimer’s disease, and blockade of miR-155 can improve some features of key disease processes suggesting it could be an important therapeutic target [ 52 – 54 ]. In addition to having a role in age-related neurodegenerative diseases, overexpression of miR-155 in T-lymphocytes reduces the lifespan of miR-146a −/− mice in a model of chronic inflammation, and recent studies show that aged miR-155 −/− mice have less spontaneous pain and decreased mortality after experimental spinal cord injury than do normal mice [ 55 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Systemic Listeria monocytogenes infection in aged mice induces long-term neuroinflammation: the role of miR-155

Cassidy¹,

Sonntag

Leenen

et al. 2022

Immun Ageing

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Background Understanding mechanisms of pathologic neuroinflammation is essential for improving outcomes after central nervous system infections. Brain tissue-resident memory T cells (bTRM) are recruited during central nervous system infection and promote pathogen control as well as noxious inflammation. Our prior studies in young mice showed optimal recruitment of CD8+ bTRM during neuroinvasive Listeria monocytogenes (Lm) infection required miR-155, and was significantly inhibited by anti-miR-155 oligonucleotides. Since Lm is an important pathogen in the elderly, we hypothesized anti-miR-155 would also inhibit accumulation of CD8+ bTRM in aged mice infected with Lm. Methods Young (2 mo) and aged (> 18 mo) male C57BL/6 mice were infected intra-peritoneally with wild-type Lm, or avirulent Lm mutants lacking the genes required for intracellular motility (ΔactA) or phagosomal escape (Δhly), then were given antibiotics. Brain leukocytes and their intracellular cytokine production were quantified by flow cytometry >28d post-infection (p.i.). The role of miR-155 was tested by injecting mice with anti-miR-155 or control oligonucleotides along with antibiotics. Results Aged mice had significantly more homeostatic CD8+ bTRM than did young mice, which did not increase after infection with wild-type Lm despite 50% mortality, whereas young mice suffered no mortality after a larger inoculum. For direct comparison of post-infectious neuroinflammation after the same inoculum, young and aged mice were infected with 107 CFU ΔactA Lm. This mutant caused no mortality and significantly increased CD8+ bTRM 28d p.i. in both groups, whereas bone marrow-derived myeloid cells, particularly neutrophils, increased only in aged mice. Notably, anti-miR-155 reduced accumulation of brain myeloid cells in aged mice after infection, whereas CD8+ bTRM were unaffected. Conclusions Systemic infection with Lm ΔactA is a novel model for studying infection-induced brain inflammation in aged mice without excessive mortality. CD8+ bTRM increase in both young and aged mice after infection, whereas only in aged mice bone marrow-derived myeloid cells increase long-term. In aged mice, anti-miR-155 inhibits brain accumulation of myeloid cells, but not CD8+ bTRM. These results suggest young and aged mice differ in manifestations and mechanisms of infection-induced neuroinflammation and give insight for developing therapies to ameliorate brain inflammation following severe infection in the elderly.

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MiR-155: An Important Regulator of Neuroinflammation

Cited by 84 publications

References 129 publications

Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

Expression and Biological Functions of miRNAs in Chronic Pain: A Review on Human Studies

Systemic Listeria monocytogenes infection in aged mice induces long-term neuroinflammation: the role of miR-155

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