Suppression of MyD88- and TRIF-dependent signaling pathways of toll-like receptor by (−)-epigallocatechin-3-gallate, a polyphenol component of green tea

Youn, Hyung S.; Lee, Joo Y.; Saitoh, Shu‐ichi; Miyake, Kensuke; Kang, Keon Wook; Choi, Yong Jun; Hwang, Daniel

doi:10.1016/j.bcp.2006.06.021

Cited by 168 publications

(111 citation statements)

References 42 publications

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“…MyD88 recruits IL-1 receptor-associated kinase 4 (IRAK-4) and induces phosphorylation of IRAK1, resulting in activation of TNF receptor-associated factor 6 (TRAF6) and subsequent IKK␣/␤/␥ for NF-B activation or the MAPK pathway for AP-1 production. TRIF activates the downstream kinases TBK1 and IKK, leading to activation of IFN regulatory factor 3 (IRF3) (25,46). While MyD88-mediated signaling is critical for DC generation of several inflammatory cytokines, the TRIF-mediated pathway accounts primarily for DC maturation and type I IFN/Th1 cytokine production (46 -48).…”

Section: Discussionmentioning

confidence: 99%

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The Adjuvanticity of a Mannosylated Antigen Reveals TLR4 Functionality Essential for Subset Specialization and Functional Maturation of Mouse Dendritic Cells

Sheng

Kalkanidis

Pouniotis

et al. 2008

The Journal of Immunology

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The evidence that dendritic cell (DC) subsets produce differential cytokines in response to specific TLR stimulation is robust. However, the role of TLR stimulation in Ag presentation and phenotypic maturation among DC subsets is not clear. Through the adjuvanticity of a novel mannosylated Ag, mannosylated dendrimer OVA (MDO), as a pathogen-associated molecular pattern Ag, we characterized the functionality of GM-CSF/IL-4-cultured bone marrow DC and Flt3 ligand (Flt3-L) DC subsets by Ag presentation and maturation assays. It was demonstrated that both bone marrow DCs and Flt3-L DCs bound, processed, and presented MDO effectively. However, while Flt3-L CD24high (conventional CD8+ equivalent) and CD11bhigh (CD8− equivalent) DCs were adept at MDO processing by MHC class I and II pathways, respectively, CD45RA+ plasmacytoid DCs presented MDO poorly to T cells. Successful MDO presentation was largely dependent on competent TLR4 for Ag localization and morphological/phenotypic maturation of DC subsets, despite the indirect interaction of MDO with TLR4. Furthermore, Toll/IL-1 receptor-domain-containing adaptor-inducing IFN-β, but not MyD88, as a TLR4 signaling modulator was indispensable for MDO-induced DC maturation and Ag presentation. Taken together, our findings suggest that DC subsets differentially respond to a pathogen-associated molecular pattern-associated Ag depending on the intrinsic programming and TLRs expressed. Optimal functionality of DC subsets in Ag presentation necessitates concomitant TLR signaling critical for efficient Ag localization and processing.

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Section: Discussionmentioning

confidence: 99%

“…8B). To investigate the role of TRIF in MDO adjuvanticity, EGCG as a potential TRIF and MyD88 signaling pathway inhibitor was used (25). As shown in Fig.…”

Section: Trif But Not Myd88 Is a Critical Tlr Signaling Modulator Fmentioning

confidence: 99%

The Adjuvanticity of a Mannosylated Antigen Reveals TLR4 Functionality Essential for Subset Specialization and Functional Maturation of Mouse Dendritic Cells

Sheng

Kalkanidis

Pouniotis

et al. 2008

The Journal of Immunology

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“…While simple algorithms (i.e., local optima) appear to be the rule, there are also clear examples of regulatory complexity in physiology: (1) There are immune receptors for polyphenols [38] (implying incorporation of minor and environmentally unpredictable molecules in immune regulation), and (2) Th2:Th1 regulation in chickens incorporates not just carotenoids, vitamin E, and fatty acids, but interactions among them [39,40]. Two underexplored questions with large implications for PRN evolution are thus how general these complex, specific algorithms are and what conditions produce them.…”

Section: Ecological and Evolutionary Implications Of Prnsmentioning

confidence: 99%

Physiological regulatory networks: ecological roles and evolutionary constraints

Cohen

Martin

Wingfield

et al. 2012

Trends in Ecology & Evolution

182

160

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Ecological and evolutionary physiology has traditionally focused on aspects of physiology one at a time. Here, we discuss the implications of considering physiological regulatory networks (PRNs) as integrated wholes, a perspective that reveals novel roles for physiology in organismal ecology and evolution. For example, evolutionary response to changes in resource abundance might be constrained by the role of dietary micronutrients in immune response regulation, given a particular pathogen environment. Because many physiological components impact more than one process, organismal homeostasis is maintained, individual fitness is determined, and evolutionary change is constrained (or facilitated) by interactions within PRNs. We discuss how PRN structure and its system-level properties could determine both individual performance and patterns of physiological evolution. GlossaryAlternative physiological structures -Different PRN structures that would produce equivalent functional and fitness outcomes for a given species in a given environment. Which structure evolves might be largely random, but might have consequences for long-term evolution of PRN structure.Cytokines -Small cell-signalling proteins involved in intercellular communication. Regulatory cascades of cytokines are particularly critical in the immune system. Dysregulation -A breakdown over time in the ability of an individual's PRN to maintain homeostasis; possibly in response to chronic stress or infection, and possibly a root cause of aging.3 Homeostasis -A state of healthy physiological equilibrium, including appropriate anticipation of and responses to changing conditions.Integrator -A PRN molecule that has a particularly crucial role in synthesizing information (internal or external) and thereby determining multiple aspects of PRN functioning (e.g., a 'hub' or 'keystone' PRN molecule) Physiological Regulatory Network (PRN) -The network of molecules and their regulatory relationships that maintain and adjust homeostasis and facilitate performance at the wholeorganism level.PRN Molecule -PRN molecules are the subset of molecules that maintain homeostasis at the organism level via their regulatory relationships with other molecules. In most cases, these molecules are the nodes (vertices) in a PRN, and regulatory relationships between them are the links (edges). In some cases, several related molecules (e.g., circulating steroid, receptors, binding globulins) may be grouped together as a single node for measurement purposes, or gene activation may be a node in some contexts. Flexibility of node definition is common in other biological networks-for example, nodes in ecological networks can be species, groups of species, life stages, or other categories (e.g., detritus). PRN state -The concentrations of all PRN molecules at a given moment for a given individual in a particular context (e.g. age, time of year, life history stage). More generally, "changes in PRN state" describe joint adjustments in molecule concentrations in anticipation of or respo...

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“…Moreover, EGCG inhibited the activation of IFN regulatory factor 3 (IRF3) induced by LPS, poly[I:C], or the overexpression of TRIF. The inhibition of IRF3 activation by EGCG was mediated through the suppression of the kinase activity of TANK-binding kinase 1 in TRIF-dependent signalling pathways of TLR3 and TLR4 (Youn et al, 2006). These data indicate that green tea flavonoids, without the structural motif conferring Michael addition, did not inhibit TLR4 dimerization however; they can modulate both MyD88-and TRIF-dependent signalling pathways of TLRs and subsequent inflammatory target gene expression.…”

Section: Signaling Pathwaysmentioning

confidence: 77%

“…However, inhibition of IKK by curcumin plays a central role in this mechanism since the lack of phosphorylation of NF-κB suppresses binding of NF-κB to DNA sequences and as a consequence expression of genes described in vitro in inflammatory and vascular cells stimulated with LPS, staphylococcal enterotoxin A, TNF-, or IL-1 , and in vivo in models of inflammatory diseases (Chan, 1995;Hatcher et al, 2008;Jobin et al, 1999;Joe et al, 2004;Pan et al, 2000;Singh & Aggarwal, 1995). Regarding the LPS/NF-κB pathway, curcumin competes in vitro with LPS for binding to the TLR-4/myeloid differentiation factor-2 complex (Gradisar et al, 2007) and prevents TLR-4 homodimerization (Youn et al, 2006), events necessary for MyD88-dependent signalling. Further studies indicated that curcumin which contains unsaturated carbonyl group, but not resveratrol (with no unsaturated carbonyl group), inhibits TLR4 activation by interfering with receptor dimerization.…”

Section: Signaling Pathwaysmentioning

confidence: 99%

Anti-Inflammatory Role of Natural Polyphenols and Their Degradation Products

Veres¹

2012

Severe Sepsis and Septic Shock - Understanding a Serious Killer

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Suppression of MyD88- and TRIF-dependent signaling pathways of toll-like receptor by (−)-epigallocatechin-3-gallate, a polyphenol component of green tea

Cited by 168 publications

References 42 publications

The Adjuvanticity of a Mannosylated Antigen Reveals TLR4 Functionality Essential for Subset Specialization and Functional Maturation of Mouse Dendritic Cells

The Adjuvanticity of a Mannosylated Antigen Reveals TLR4 Functionality Essential for Subset Specialization and Functional Maturation of Mouse Dendritic Cells

Physiological regulatory networks: ecological roles and evolutionary constraints

Anti-Inflammatory Role of Natural Polyphenols and Their Degradation Products

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