Influence of olive-derived hydroxytyrosol on the toll-like receptor 4-dependent inflammatory response of mouse peritoneal macrophages

Objective The present study aimed to evaluate the effects of cluster of differentiation (CD)4+CD25+ forkhead box p3 (Foxp3)+ regulatory T cells (Tregs) on unexplained recurrent spontaneous abortion (URSA) and the associated mechanisms. Methods The proportion of CD4+CD25+Foxp3+ Tregs and inflammatory cytokine concentrations in the peripheral blood of women with URSA were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. CBA/JxDBA/2J mating was used to establish an abortion-prone mouse model and the model mice were treated with the Toll-like receptor 4 (TLR4) antagonist E5564 and the TLR4 agonist lipopolysaccharide. Results The proportion of CD4+CD25+Foxp3+ Tregs was decreased and the inflammatory response was increased in women with URSA. In the abortion-prone mouse model, E5564 significantly increased the proportion of CD4+CD25+Foxp3+ Tregs, decreased the inflammatory response, and increased Foxp3 mRNA and protein expression. Lipopolysaccharide had adverse effects on the abortion-prone model. Conclusions These data suggest that CD4+CD25+Foxp3+ Tregs regulate immune homeostasis in URSA via the TLR4/nuclear factor-κB pathway, and that the TLR4 antagonist E5564 may be a novel and potential drug for treating URSA.

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Paralemmin-3 contributes to lipopolysaccharide-induced inflammatory response and is involved in lipopolysaccharide-Toll-like receptor-4 signaling in alveolar macrophages

International Journal of Molecular Medicine ◽

10.3892/ijmm.2017.3161 ◽

2017 ◽

Author(s):

Xu-Xin Chen ◽

Lu Tang ◽

Yu-Mei Fu ◽

Yi Wang ◽

Zhi-Hai Han ◽

...

Keyword(s):

Inflammatory Response ◽

Alveolar Macrophages ◽

Toll Like Receptor ◽

Toll Like Receptor 4

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Key Player in Cardiac Hypertrophy, Emphasizing the Role of Toll-Like Receptor 4

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2020.579036 ◽

2020 ◽

Vol 7 ◽

Author(s):

Zheng Xiao ◽

Bin Kong ◽

Hongjie Yang ◽

Chang Dai ◽

Jin Fang ◽

...

Keyword(s):

Inflammatory Response ◽

Cardiac Hypertrophy ◽

Intracellular Signaling ◽

Molecular Mechanisms ◽

New Technologies ◽

Immune Cell ◽

Current Knowledge ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Tlr4 Signaling

Toll-like receptor 4 (TLR4), a key pattern recognition receptor, initiates the innate immune response and leads to chronic and acute inflammation. In the past decades, accumulating evidence has implicated TLR4-mediated inflammatory response in regulation of myocardium hypertrophic remodeling, indicating that regulation of the TLR4 signaling pathway may be an effective strategy for managing cardiac hypertrophy's pathophysiology. Given TLR4's significance, it is imperative to review the molecular mechanisms and roles underlying TLR4 signaling in cardiac hypertrophy. Here, we comprehensively review the current knowledge of TLR4-mediated inflammatory response and its interaction ligands and co-receptors, as well as activation of various intracellular signaling. We also describe the associated roles in promoting immune cell infiltration and inflammatory mediator secretion, that ultimately cause cardiac hypertrophy. Finally, we provide examples of some of the most promising drugs and new technologies that have the potential to attenuate TLR4-mediated inflammatory response and prevent or reverse the ominous cardiac hypertrophy outcomes.

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Bacteroides fragilis-Derived Lipopolysaccharide Produces Cell Activation and Lethal Toxicity via Toll-Like Receptor 4

Infection and Immunity ◽

10.1128/iai.73.9.5620-5627.2005 ◽

2005 ◽

Vol 73 (9) ◽

pp. 5620-5627 ◽

Cited By ~ 43

Author(s):

Giuseppe Mancuso ◽

Angelina Midiri ◽

Carmelo Biondo ◽

Concetta Beninati ◽

Maria Gambuzza ◽

...

Keyword(s):

Cell Activation ◽

Cytokine Production ◽

Biological Activities ◽

Endotoxic Shock ◽

Intestinal Flora ◽

Bacteroides Fragilis ◽

Peritoneal Macrophages ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

In Cells

ABSTRACT Bacteroides fragilis, which is part of the normal intestinal flora, is a frequent cause of serious disease, especially in diabetic and surgical patients. In these conditions, B. fragilis lipopolysaccharide (LPS) is likely to play a major pathophysiologic role. B. fragilis LPS is structurally different from classical enterobacterial LPS, whose biological activities are mediated by Toll-like receptor 4 (TLR4) activation. The ability of B. fragilis LPS to activate TLR4 and TLR2 was investigated here, since evidence on this issue is scarce and controversial. Each of four different protein-free B. fragilis LPS preparations could induce interleukin-8 responses in cells cotransfected with TLR4/CD14/MD2 but not TLR4/CD14 alone. Two of the preparations also induced cytokine production in cells cotransfected with TLR2/CD14 or in peritoneal macrophages from TLR4 mutant C3H/HeJ mice. Both of these activities, however, were lost after repurification with a modified phenol reextraction procedure. Importantly, all preparations could induce endotoxic shock in TLR2-deficient mice, but not in TLR4 mutant C3H/HeJ mice. Consistent with these findings, anti-TLR4 and anti-CD14, but not anti-TLR2, antibodies could inhibit B. fragilis LPS-induced cytokine production in human monocytes. Collectively, these results indicate that B. fragilis LPS signals via a TLR4/CD14/MD2-dependent pathway, and it is unable to activate TLR2. Moreover, our data document the occurrence of TLR2-activating contaminants even in highly purified B. fragilis LPS preparations. This may explain earlier contradictory findings on the ability of B. fragilis LPS to activate cells in the absence of functional TLR4. These data may be useful to devise strategies to prevent the pathophysiologic changes observed during B. fragilis sepsis and to better understand structure-activity relationships of LPS.

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Immunomodulatory Effects of Yersinia pestis Lipopolysaccharides on Human Macrophages

Clinical and Vaccine Immunology ◽

10.1128/cvi.00336-09 ◽

2009 ◽

Vol 17 (1) ◽

pp. 49-55 ◽

Cited By ~ 20

Author(s):

Motohiro Matsuura ◽

Hideyuki Takahashi ◽

Haruo Watanabe ◽

Shinji Saito ◽

Kazuyoshi Kawahara

Keyword(s):

Inflammatory Response ◽

Yersinia Pestis ◽

Lipid A ◽

Antagonistic Activity ◽

Gram Negative Bacteria ◽

Toll Like Receptor ◽

Defense System ◽

Toll Like Receptor 4 ◽

Bacterial Binding ◽

Binding Forms

ABSTRACTIn the current study, we investigated the activity of lipopolysaccharide (LPS) purified fromYersinia pestisgrown at either 27°C or 37°C (termed LPS-27 and LPS-37, respectively). LPS-27 containing hexa-acylated lipid A, similar to the LPS present in usual gram-negative bacteria, stimulated an inflammatory response in human U937 cells through Toll-like receptor 4 (TLR4). LPS-37, which did not contain hexa-acylated lipid A, exhibited strong antagonistic activity to the TLR4-mediated inflammatory response. The phagocytic activity in the cells was not affected by LPS-37. To estimate the activity of LPS in its bacterial binding form, formalin-killed bacteria (FKB) were prepared fromY. pestiscells grown at 27°C or 37°C (termed FKB-27 and FKB-37, respectively). FKB-27 strongly stimulated the inflammatory response. This activity was suppressed in the presence of an anti-TLR4 antibody but not an anti-TLR2 antibody. In addition, this activity was almost completely suppressed by LPS-37, indicating that the activity of FKB-27 is predominantly derived from the LPS-27 bacterial binding form. In contrast, FKB-37 showed no antagonistic activity. The results arising from the current study indicate thatY. pestiscauses infection in humans without stimulating the TLR4-based defense systemviabacterial binding of LPS-37, even when bacterial free LPS-37 is not released to suppress the defense system. This is in contrast to the findings for bacteria that possess agonistic LPS types, which are easily recognized by the defense systemviathe bacterial binding forms.

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