Topology, dynamics, and heterogeneity in immune signaling

Webb, James; Behar, Marcelo

doi:10.1002/wsbm.1306

Cited by 5 publications

(4 citation statements)

References 109 publications

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“…The LRRs motif is responsible for pathogen recognition, whereas the TIR domain interacts with signal transduction adaptors and initiates signaling. This family of receptors is distinctly important for pathogen recognition by the innate immune system [67,68].…”

Section: Overview About Tlr-4 Structure and Expressionmentioning

confidence: 99%

The Emerging Role of Curcumin in the Modulation of TLR-4 Signaling Pathway: Focus on Neuroprotective and Anti-Rheumatic Properties

Panaro

Corrado

Benameur

et al. 2020

IJMS

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Natural products have been used in medicine for thousands of years. Given their potential health benefits, they have gained significant popularity in recent times. The administration of phytochemicals existed shown to regulate differential gene expression and modulate various cellular pathways implicated in cell protection. Curcumin is a natural dietary polyphenol extracted from Curcuma Longa Linn with different biological and pharmacological effects. One of the important targets of curcumin is Toll-like receptor-4 (TLR-4), the receptor which plays a key role in the modulation of the immune responses and the stimulation of inflammatory chemokines and cytokines production. Different studies have demonstrated that curcumin attenuates inflammatory response via TLR-4 acting directly on receptor, or by its downstream pathway. Curcumin bioavailability is low, so the use of exosomes, as nano drug delivery, could improve the efficacy of curcumin in inflammatory diseases. The focus of this review is to explore the therapeutic effect of curcumin interacting with TLR-4 receptor and how this modulation could improve the prognosis of neuroinflammatory and rheumatic diseases.

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Section: Overview About Tlr-4 Structure and Expressionmentioning

confidence: 99%

The Emerging Role of Curcumin in the Modulation of TLR-4 Signaling Pathway: Focus on Neuroprotective and Anti-Rheumatic Properties

Panaro

Corrado

Benameur

et al. 2020

IJMS

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“…For example, pathogen recognition is performed by the LRR motif, while signal initiation is performed by interaction of the TIR domain with the signal transduction adaptors. This receptor family is extremely important for pathogen recognition by the innate immune system ( 60 , 61 ). Recently, several reports have indicated the association between cancer and TLRs.…”

Section: Tlr/nf-κb/nlrp Signaling Pathway In Cancer Initiation and Pr...mentioning

confidence: 99%

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

et al. 2022

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BackgroundTumors often progress to a more aggressive phenotype to resist drugs. Multiple dysregulated pathways are behind this tumor behavior which is known as cancer chemoresistance. Thus, there is an emerging need to discover pivotal signaling pathways involved in the resistance to chemotherapeutic agents and cancer immunotherapy. Reports indicate the critical role of the toll-like receptor (TLR)/nuclear factor-κB (NF-κB)/Nod-like receptor pyrin domain-containing (NLRP) pathway in cancer initiation, progression, and development. Therefore, targeting TLR/NF-κB/NLRP signaling is a promising strategy to augment cancer chemotherapy and immunotherapy and to combat chemoresistance. Considering the potential of phytochemicals in the regulation of multiple dysregulated pathways during cancer initiation, promotion, and progression, such compounds could be suitable candidates against cancer chemoresistance.ObjectivesThis is the first comprehensive and systematic review regarding the role of phytochemicals in the mitigation of chemoresistance by regulating the TLR/NF-κB/NLRP signaling pathway in chemotherapy and immunotherapy.MethodsA comprehensive and systematic review was designed based on Web of Science, PubMed, Scopus, and Cochrane electronic databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to include papers on TLR/NF-κB/NLRP and chemotherapy/immunotherapy/chemoresistance by phytochemicals.ResultsPhytochemicals are promising multi-targeting candidates against the TLR/NF-κB/NLRP signaling pathway and interconnected mediators. Employing phenolic compounds, alkaloids, terpenoids, and sulfur compounds could be a promising strategy for managing cancer chemoresistance through the modulation of the TLR/NF-κB/NLRP signaling pathway. Novel delivery systems of phytochemicals in cancer chemotherapy/immunotherapy are also highlighted.ConclusionTargeting TLR/NF-κB/NLRP signaling with bioactive phytocompounds reverses chemoresistance and improves the outcome for chemotherapy and immunotherapy in both preclinical and clinical stages.

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“…Analytical techniques available to infer the network interactions underlying the gene expression dynamics require extensive experimental assessments of responses to targeted gene perturbations [12]. The utility of combining time-series analysis with network-based approaches has been demonstrated extensively in developmental biology [13, 14], immunology [15–17], neural systems [18, 19], and critical care medicine [20, 21]. Interactions between dynamics and structure have also been studied in mechanical, electrical, telecommunication, social, and economic networks [22].…”

Section: Introductionmentioning

confidence: 99%

A data-driven modeling approach to identify disease-specific multi-organ networks driving physiological dysregulation

et al. 2017

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Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension). We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences. We obtained experimental data on the expression of 22 genes across five organs, over a time span that encompassed the development of autonomic nervous system dysfunction and hypertension. We pursued a unique approach for identification of continuous-time models that jointly described the dynamics and structure of multi-organ networks by estimating a sparse subset of ∼12,000 possible gene regulatory interactions. Our analyses revealed that an autonomic dysfunction-specific multi-organ sequence of gene expression activation patterns was associated with a distinct gene regulatory network. We analyzed the model structures for adaptation motifs, and identified disease-specific network motifs involving genes that exhibited aberrant temporal dynamics. Bioinformatic analyses identified disease-specific single nucleotide variants within or near transcription factor binding sites upstream of key genes implicated in maintaining physiological homeostasis. Our approach illustrates a novel framework for investigating the pathogenesis through model-based analysis of multi-organ system dynamics and network properties. Our results yielded novel candidate molecular targets driving the development of cardiovascular disease, metabolic syndrome, and immune dysfunction.

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Topology, dynamics, and heterogeneity in immune signaling

Cited by 5 publications

References 109 publications

The Emerging Role of Curcumin in the Modulation of TLR-4 Signaling Pathway: Focus on Neuroprotective and Anti-Rheumatic Properties

The Emerging Role of Curcumin in the Modulation of TLR-4 Signaling Pathway: Focus on Neuroprotective and Anti-Rheumatic Properties

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

A data-driven modeling approach to identify disease-specific multi-organ networks driving physiological dysregulation

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