Macrophage Inflammatory Protein-3 Alpha (MIP-3α)/CCL20 in HIV-1- Infected Individuals

Aziz, Najib; Detels, Roger; Chang, Li‐Te; Butch, Anthony W.

doi:10.4172/2155-6113.1000587

Cited by 15 publications

(11 citation statements)

References 45 publications

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“…Lee et al and Baba et al suggested that CCL20 was upregulated during inflammation and elicited its effects on its target cells by binding to and activating the chemokine receptor CCR6 ( 69 , 70 ). During HIV infection, CCL20 has been shown to remain elevated throughout the course of the disease; the median CCL20 serum level was approximately 3.3-fold higher in HIV-infected individuals than in uninfected individuals and was negatively correlated with CD4 + T cell count ( 63 , 71 ).…”

Section: Chemokines and Chemokine Receptors Related To Hiv Replicatiomentioning

confidence: 99%

Chemokines and Chemokine Receptors: Accomplices for Human Immunodeficiency Virus Infection and Latency

2017

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Chemokines are small chemotactic cytokines that are involved in the regulation of immune cell migration. Multiple functional properties of chemokines, such as pro-inflammation, immune regulation, and promotion of cell growth, angiogenesis, and apoptosis, have been identified in many pathological and physiological contexts. Human immunodeficiency virus (HIV) infection is characterized by persistent inflammation and immune activation during both acute and chronic phases, and the “cytokine storm” is one of the hallmarks of HIV infection. Along with immune activation after HIV infection, an extensive range of chemokines and other cytokines are elevated, thereby generating the so-called “cytokine storm.” In this review, the effects of the upregulated chemokines and chemokine receptors on the processes of HIV infection are discussed. The objective of this review was to focus on the main chemokines and chemokine receptors that have been found to be associated with HIV infection and latency. Elevated chemokines and chemokine receptors have been shown to play important roles in the HIV life cycle, disease progression, and HIV reservoir establishment. Thus, targeting these chemokines and receptors and the other proteins of related signaling pathways might provide novel therapeutic strategies, and the evidence indicates a promising future regarding the development of a functional cure for HIV.

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Section: Chemokines and Chemokine Receptors Related To Hiv Replicatiomentioning

confidence: 99%

Chemokines and Chemokine Receptors: Accomplices for Human Immunodeficiency Virus Infection and Latency

2017

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“…Higher levels of this cytotoxic defensin protein that is contained within neutrophil granules have been reported in IA tissue, suggesting that production of this protein may occur peripherally before neutrophils enter the IA wall [ 72 ]. Here the molecules CCR4 (which is a receptor of MIP-1 , RANTES , CCL17 , and MCP-1 ) [ 73 , 74 ] and CCR6 (which is a receptor of MIP-3α ) [ 75 ] were also related to the TNF node. We suspect that these receptors, which play a role in dendritic and T cell migration and recruitment during inflammation, [ 76 ] may coordinate inflammatory cell migration once expressed in aneurysm tissue.…”

Section: Discussionmentioning

confidence: 99%

Classification models using circulating neutrophil transcripts can detect unruptured intracranial aneurysm

et al. 2020

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Background Intracranial aneurysms (IAs) are dangerous because of their potential to rupture. We previously found significant RNA expression differences in circulating neutrophils between patients with and without unruptured IAs and trained machine learning models to predict presence of IA using 40 neutrophil transcriptomes. Here, we aim to develop a predictive model for unruptured IA using neutrophil transcriptomes from a larger population and more robust machine learning methods. Methods Neutrophil RNA extracted from the blood of 134 patients (55 with IA, 79 IA-free controls) was subjected to next-generation RNA sequencing. In a randomly-selected training cohort (n = 94), the Least Absolute Shrinkage and Selection Operator (LASSO) selected transcripts, from which we constructed prediction models via 4 well-established supervised machine-learning algorithms (K-Nearest Neighbors, Random Forest, and Support Vector Machines with Gaussian and cubic kernels). We tested the models in the remaining samples (n = 40) and assessed model performance by receiver-operating-characteristic (ROC) curves. Real-time quantitative polymerase chain reaction (RT-qPCR) of 9 IA-associated genes was used to verify gene expression in a subset of 49 neutrophil RNA samples. We also examined the potential influence of demographics and comorbidities on model prediction. Results Feature selection using LASSO in the training cohort identified 37 IA-associated transcripts. Models trained using these transcripts had a maximum accuracy of 90% in the testing cohort. The testing performance across all methods had an average area under ROC curve (AUC) = 0.97, an improvement over our previous models. The Random Forest model performed best across both training and testing cohorts. RT-qPCR confirmed expression differences in 7 of 9 genes tested. Gene ontology and IPA network analyses performed on the 37 model genes reflected dysregulated inflammation, cell signaling, and apoptosis processes. In our data, demographics and comorbidities did not affect model performance. Conclusions We improved upon our previous IA prediction models based on circulating neutrophil transcriptomes by increasing sample size and by implementing LASSO and more robust machine learning methods. Future studies are needed to validate these models in larger cohorts and further investigate effect of covariates.

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“…Though IL-6 production can be initiated by IL-1β induced transactivation of NF-κB, a single 24 hr N9 exposure may not be sufficient to significantly increase CVL secretion of IL-6, as previously reported by Fichorova and co-workers [18], which was in agreement with the results observed in the current study. Since the presence of IL-1β, IL-8, TNFα and MIP-3α can result in an influx and activation of HIV-susceptible cells at the vaginal mucosa including T cells [60], macrophages, and Langerhans cells [61], we further assessed the levels of these markers in different sections of the rabbit vagina. Similarly, N9-enhanced protein expression of these mediators in vaginal tissue were mitigated in the presence of HCQ (Fig.…”

Section: Discussionmentioning

confidence: 99%

Implant delivering hydroxychloroquine attenuates vaginal T lymphocyte activation and inflammation

Chen

Traoré

Yang

et al. 2018

Journal of Controlled Release

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Evidence suggests that women who are naturally resistant to HIV infection exhibit low baseline immune activation at the female genital tract (FGT). This "immune quiescent" state is associated with lower expression of T-cell activation markers, reduced levels of gene transcription and pro-inflammatory cytokine or chemokine production involved in HIV infection while maintaining an intact immune response against pathogens. Therefore, if this unique immune quiescent state can be pharmacologically induced locally, it will provide an excellent women-oriented strategy against HIV infection To our knowledge, this is the first research article evaluating in vivo, an innovative trackable implant that can provide controlled delivery of hydroxychloroquine (HCQ) to successfully attenuate vaginal T lymphocyte activation and inflammation in a rabbit model as a potential strategy to induce an "immune quiescent" state within the FGT for the prevention of HIV infection. This biocompatible implant can deliver HCQ above therapeutic concentrations in a controlled manner, reduce submucosal immune cell recruitment, improve mucosal epithelium integrity, decrease protein and gene expression of T-cell activation markers, and attenuate the induction of key pro-inflammatory mediators. Our results suggest that microbicides designed to maintain a low level of immune activation at the FGT may offer a promising new strategy for reducing HIV infection.

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Macrophage Inflammatory Protein-3 Alpha (MIP-3α)/CCL20 in HIV-1- Infected Individuals

Cited by 15 publications

References 45 publications

Chemokines and Chemokine Receptors: Accomplices for Human Immunodeficiency Virus Infection and Latency

Chemokines and Chemokine Receptors: Accomplices for Human Immunodeficiency Virus Infection and Latency

Classification models using circulating neutrophil transcripts can detect unruptured intracranial aneurysm

Implant delivering hydroxychloroquine attenuates vaginal T lymphocyte activation and inflammation

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