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

Background Ischemia-reperfusion (I-R) injury is a sterile inflammatory process that is commonly associated with diverse clinical situations such as hemorrhage followed by resuscitation, transient embolic events, and organ transplantation. I-R injury can induce lung dysfunction whether the I-R occurs in the lung or in a remote organ. Recently, evidence has emerged that receptors and pathways of the innate immune system are involved in recognizing sterile inflammation and overlap considerably with those involved in the recognition of and response to pathogens. Methods The authors used a mouse surgical model of transient unilateral left pulmonary artery occlusion without bronchial involvement to create ventilated lung I-R injury. In addition, they mimicked nutritional I-R injury in vitro by transiently depriving cells of all nutrients. Results Compared with sham-operated mice, mice subjected to ventilated lung I-R injury had up-regulated lung expression of inflammatory mediator messenger RNA for interleukin-1β, interleukin-6, and chemokine (C-X-C motif) ligand-1 and -2, paralleled by histologic evidence of lung neutrophil recruitment and increased plasma concentrations of interleukin-1β, interleukin-6, and high-mobility group protein B1 proteins. This inflammatory response to I-R required toll-like receptor-4 (TLR4). In addition, the authors demonstrated in vitro cooperativity and cross-talk between human macrophages and endothelial cells, resulting in augmented inflammatory responses to I-R. Remarkably, the authors found that selective depletion of alveolar macrophages rendered mice resistant to ventilated lung I-R injury. Conclusions The data reveal that alveolar macrophages and the pattern recognition receptor toll-like receptor-4 are involved in the generation of the early inflammatory response to lung I-R injury.

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CD4+CD25+Foxp3+ regulatory T cells regulate immune balance in unexplained recurrent spontaneous abortion via the Toll-like receptor 4/nuclear factor-κB pathway

Journal of International Medical Research ◽

10.1177/0300060520980940 ◽

2020 ◽

Vol 48 (12) ◽

pp. 030006052098094

Author(s):

Shuang Qin ◽

Li Li ◽

Jia Liu ◽

Jinrui Zhang ◽

Qing Xiao ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Inflammatory Response ◽

Mouse Model ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Unexplained Recurrent Spontaneous Abortion ◽

Tlr4 Antagonist

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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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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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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Toll-like receptor 4 plays a crucial role in the immune-adrenal response to systemic inflammatory response syndrome

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0601527103 ◽

2006 ◽

Vol 103 (16) ◽

pp. 6392-6397 ◽

Cited By ~ 95

Author(s):

K. Zacharowski ◽

P. A. Zacharowski ◽

A. Koch ◽

A. Baban ◽

N. Tran ◽

...

Keyword(s):

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Crucial Role ◽

Systemic Inflammatory Response ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Adrenal Response

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Amyloid-beta mediates the receptor of advanced glycation end product-induced pro-inflammatory response via toll-like receptor 4 signaling pathway in retinal ganglion cell line RGC-5

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2015.03.002 ◽

2015 ◽

Vol 64 ◽

pp. 1-10 ◽

Cited By ~ 11

Author(s):

Jong-Jer Lee ◽

Pei-Wen Wang ◽

I-Hui Yang ◽

Chia-Lin Wu ◽

Jiin-Haur Chuang

Keyword(s):

Inflammatory Response ◽

Ganglion Cell ◽

Cell Line ◽

Retinal Ganglion Cell ◽

Amyloid Beta ◽

Retinal Ganglion ◽

Toll Like Receptor ◽

Advanced Glycation ◽

Toll Like Receptor 4 ◽

Advanced Glycation End Product

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Glycosaminoglycans reduced inflammatory response by modulating toll-like receptor-4 in LPS-stimulated chondrocytes

Archives of Biochemistry and Biophysics ◽

10.1016/j.abb.2009.09.017 ◽

2009 ◽

Vol 491 (1-2) ◽

pp. 7-15 ◽

Cited By ~ 37

Author(s):

Giuseppe M. Campo ◽

Angela Avenoso ◽

Salvatore Campo ◽

Paola Traina ◽

Angela D’Ascola ◽

...

Keyword(s):

Inflammatory Response ◽

Toll Like Receptor ◽

Toll Like Receptor 4

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Activation of Porcine Alveolar Macrophages byActinobacillus pleuropneumoniaeLipopolysaccharide via the Toll-Like Receptor 4/NF-κB-Mediated Pathway

Infection and Immunity ◽

10.1128/iai.00642-17 ◽

2017 ◽

Vol 86 (3) ◽

Cited By ~ 2

Author(s):

Bi Li ◽

Jing Fang ◽

Zhicai Zuo ◽

Sirui Yin ◽

Tingting He ◽

...

Keyword(s):

Proinflammatory Cytokines ◽

Alveolar Macrophages ◽

Intracellular Signaling ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Necrosis Factor Alpha ◽

Content Type ◽

Immunological Responses ◽

Pathogen Invasion ◽

Porcine Contagious Pleuropneumonia

ABSTRACTActinobacillus pleuropneumoniaeis the causative agent of porcine contagious pleuropneumonia. Overproduction of proinflammatory cytokines, like interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, and resistin, in the lung is an important feature ofA. pleuropneumoniaeinfection. These proinflammatory cytokines enhance inflammatory and immunological responses. However, the mechanism that leads to cytokine production remains unclear. As a major virulence factor ofA. pleuropneumoniae, lipopolysaccharide (LPS) may act as a potent stimulator of Toll-like receptor 4 (TLR4), triggering a number of intracellular signaling pathways that lead to the synthesis of proinflammatory cytokines. Porcine alveolar macrophages (PAMs) are the first line of defense against pathogenic microbes during pathogen invasion. The results of the present study demonstrate thatA. pleuropneumoniaeLPS induces PAMs to produce inflammatory cytokines in time- and dose-dependent manners. Moreover, PAMs were activated byA. pleuropneumoniaeLPS, resulting in upregulation of signaling molecules, including TLR4, MyD88, TRIF-related adaptor molecule, and NF-κB. In contrast, the activation effects ofA. pleuropneumoniaeLPS on PAMs could be suppressed by specific inhibitors, like small interfering RNA and Bay11-7082. Taken together, our data indicate thatA. pleuropneumoniaeLPS can induce PAMs to produce proinflammatory cytokines via the TLR4/NF-κB-mediated pathway. These findings partially reveal the mechanism of the overproduction of proinflammatory cytokines in the lungs of swine withA. pleuropneumoniaeinfection and may provide targets for the prevention ofA. pleuropneumoniae-induced pneumonia. All the data could be used as a reference for the pathogenesis of respiratory infection.

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