A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs

Huik, Kristi; Avi, Radko; Pauskar, Merit; Kallas, Eveli; Jõgeda, Ene Ly; Karki, Tõnis; Talu, Ave; Abel-Ollo, Katri; Uusküla, Anneli; Carrillo, Andrew; Ahuja, Sunil K.; He, Weijing; Lutsar, Irja

doi:10.1371/journal.pone.0156850

Cited by 3 publications

(1 citation statement)

References 32 publications

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“…Till date, genetic studies associating host genotype and JE are limited only to the analysis of TNFα and TLR3 polymorphisms 28 , 29 . rs1024611G and rs2280788G are associated with communicable diseases like pulmonary tuberculosis 30 , 31 and Hepatitis C 32 , 33 . Not only in infectious diseases, transition of adenine (A) to guanine (G) at CCL2 (−2518) locus i.e.…”

Section: Discussionmentioning

confidence: 99%

Significance of CCL2, CCL5 and CCR2 polymorphisms for adverse prognosis of Japanese encephalitis from an endemic population of India

Chowdhury

Khan

2017

Sci Rep

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Japanese encephalitis (JE) is a major contributor for viral encephalitis in Asia. Vaccination programme has limited success for largely populated JE endemic countries like India and disease exposure is unavoidable. Involvement of chemokines and its co-receptors for adverse prognosis of JE have been documented both in vitro and in vivo. Identification of the genetic predisposing factor for JE infection in humans is crucial but not yet established. Therefore, we investigated the association of single nucleotide polymorphisms (SNPs) in chemokines (CCL2 and CCL5) and its co-receptors (CCR2 and CCR5) with their protein level for JE. The study enrolled 87 symptomatic JE cases (mild: severe = 24:63) and 94 asymptomatic controls. Our study demonstrated that CCL2 (rs1024611G), CCL5 (rs2280788G) and CCR2 (rs1799864A) significantly associated with JE (Odds ratio = 1.63, 2.95 and 2.62, respectively and P = 0.045, P = 0.05 and P = 0.0006, respectively). The study revealed that rs1024611G allele was associated with elevated level of CCL2. CCL5 elevation associated with JE mortality having a Cox proportional hazard of 1.004 (P = 0.033). In conclusion, SNPs of chemokine viz. CCL2 (rs1024611G) and its receptor CCR2 (rs1799864A) significantly associated with JE which may serve as possible genetic predisposing factor and CCL5 protein level may act as marker for disease survival.

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Section: Discussionmentioning

confidence: 99%

Significance of CCL2, CCL5 and CCR2 polymorphisms for adverse prognosis of Japanese encephalitis from an endemic population of India

Chowdhury

Khan

2017

Sci Rep

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Association of genetic polymorphisms of chemokines and their receptors with clearance or persistence of hepatitis C virus infection

El-Bendary

Neamatallah

Elalfy

et al. 2018

British Journal of Biomedical Science

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mTOR Signaling Pathway Regulates the Release of Proinflammatory Molecule CCL5 Implicated in the Pathogenesis of Autism Spectrum Disorder

Wang

Qin

et al. 2022

Front. Immunol.

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Autism spectrum disorder (ASD) is a complex pervasive neurodevelopmental disorder and neuroinflammation may contribute to the pathogenesis of ASD. However, the exact mechanisms of abnormal release of proinflammatory mediators in ASD remain poorly understood. This study reports elevated plasma levels of the proinflammatory chemokine (C-C motif) ligand 5 (CCL5) in children with ASD, suggesting an aberrant inflammatory response appearing in the development of ASD. Mining of the expression data of brain or blood tissue from individuals with ASD reveals that mTOR signaling is aberrantly activated in ASD patients. Our in vitro study shows that suppression of mTOR reduces the gene expression and release of CCL5 from human microglia, supporting that CCL5 expression is regulated by mTOR activity. Furthermore, bacterial lipopolysaccharide (LPS)-induced CCL5 expression can be counteracted by siRNA against NF-κB, suggests a determining role of NF-κB in upregulating CCL5 expression. However, a direct regulatory relationship between the NF-κB element and the mTOR signaling pathway was not observed in rapamycin-treated cells. Our results show that the phosphorylated CREB can be induced to suppress CCL5 expression by outcompeting NF-κB in binding to CREB-binding protein (CREBBP) once the mTOR signaling pathway is inhibited. We propose that the activation of mTOR signaling in ASD may induce the suppression of phosphorylation of CREB, which in turn results in the increased binding of CREBBP to NF-κB, a competitor of phosphorylated CREB to drive expression of CCL5. Our study sheds new light on the inflammatory mechanisms of ASD and paves the way for the development of therapeutic strategy for ASD.

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A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs

Cited by 3 publications

References 32 publications

Significance of CCL2, CCL5 and CCR2 polymorphisms for adverse prognosis of Japanese encephalitis from an endemic population of India

Significance of CCL2, CCL5 and CCR2 polymorphisms for adverse prognosis of Japanese encephalitis from an endemic population of India

Association of genetic polymorphisms of chemokines and their receptors with clearance or persistence of hepatitis C virus infection

mTOR Signaling Pathway Regulates the Release of Proinflammatory Molecule CCL5 Implicated in the Pathogenesis of Autism Spectrum Disorder

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