scholarly journals SARS-CoV-2 spike protein S1 subunit induces pro-inflammatory responses via toll-like receptor 4 signaling in murine and human macrophages

Heliyon ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e06187 ◽  
Author(s):  
Ken Shirato ◽  
Takako Kizaki
Keyword(s):  
Inflammatory Responses ◽  
Spike Protein ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Human Macrophages

scholarly journals Biofilm Growth Increases Phosphorylcholine Content and Decreases Potency of Nontypeable Haemophilus influenzae Endotoxins

2006 ◽  
Vol 74 (3) ◽  
pp. 1828-1836 ◽  
Author(s):  
Shayla West-Barnette ◽  
Andrea Rockel ◽  
W. Edward Swords
Keyword(s):  
Haemophilus Influenzae ◽  
Inflammatory Responses ◽  
Opportunistic Pathogen ◽  
Host Responses ◽  
Toll Like Receptor ◽  
Nontypeable Haemophilus Influenzae ◽  
Toll Like Receptor 4 ◽  
Biofilm Growth ◽  
Bacterial Endotoxins ◽  
Cell Layers

ABSTRACT Nontypeable Haemophilus influenzae (NTHI) is a common respiratory commensal and opportunistic pathogen. NTHI is normally contained within the airways by host innate defenses that include recognition of bacterial endotoxins by Toll-like receptor 4 (TLR4). NTHI produces lipooligosaccharide (LOS) endotoxins which lack polymeric O side chains and which may contain host glycolipids. We recently showed that NTHI biofilms contain variants with sialylated LOS glycoforms that are essential to biofilm formation. In this study, we show that NTHI forms biofilms on epithelial cell layers. Confocal analysis revealed that sialylated variants were distributed throughout the biofilm, while variants expressing phosphorylcholine (PCho) were found within the biofilm. Consistent with this observation, PCho content of LOS purified from NTHI biofilms was increased compared to LOS from planktonic cultures. Hypothesizing that the observed changes in endotoxin composition could affect bioactivity, we compared inflammatory responses to NTHI LOS purified from biofilm and planktonic cultures. Our results show that endotoxins from biofilms induced weaker host innate responses. While we observed a minimal effect of sialylation on LOS bioactivity, there was a significant decrease in bioactivity associated with PCho substitutions. We thus conclude that biofilm growth increases the proportion of PCho+ variants in an NTHI population, resulting in a net decrease in LOS bioactivity. Thus, in addition to their well-documented resistance phenotypes, our data show that biofilm communities of NTHI bacteria contain variants that evoke less potent host responses.

scholarly journals Human resistin protects against endotoxic shock by blocking LPS–TLR4 interaction

2017 ◽  
Vol 114 (48) ◽  
pp. E10399-E10408 ◽  
Author(s):  
Jessica C. Jang ◽  
Jiang Li ◽  
Luca Gambini ◽  
Hashini M. Batugedara ◽  
Sandeep Sati ◽  
...  
Keyword(s):  
Immune Cell ◽  
Inflammatory Responses ◽  
Endotoxic Shock ◽  
Critical Role ◽  
Nippostrongylus Brasiliensis ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Therapeutic Function ◽  
Human Immune ◽  
Human Resistin

Helminths trigger multiple immunomodulatory pathways that can protect from sepsis. Human resistin (hRetn) is an immune cell-derived protein that is highly elevated in helminth infection and sepsis. However, the function of hRetn in sepsis, or whether hRetn influences helminth protection against sepsis, is unknown. Employing hRetn-expressing transgenic mice (hRETNTg+) and recombinant hRetn, we identify a therapeutic function for hRetn in lipopolysaccharide (LPS)-induced septic shock. hRetn promoted helminth-induced immunomodulation, with increased survival of Nippostrongylus brasiliensis (Nb)-infected hRETNTg+ mice after a fatal LPS dose compared with naive mice or Nb-infected hRETNTg− mice. Employing immunoprecipitation assays, hRETNTg+Tlr4−/− mice, and human immune cell culture, we demonstrate that hRetn binds the LPS receptor Toll-like receptor 4 (TLR4) through its N terminal and modulates STAT3 and TBK1 signaling, triggering a switch from proinflammatory to anti-inflammatory responses. Further, we generate hRetn N-terminal peptides that are able to block LPS proinflammatory function. Together, our studies identify a critical role for hRetn in blocking LPS function with important clinical significance in helminth-induced immunomodulation and sepsis.

399 INVOLVEMENT OF TOLL LIKE RECEPTOR-4 IN INFLAMMATORY RESPONSES OF ENDOTHELIAL CELLS

2011 ◽  
Vol 12 (1) ◽  
pp. 85
Author(s):  
R. Menghini ◽  
M. Tesauro ◽  
V. Rovella ◽  
A. Marino ◽  
R. Lauro ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

scholarly journals A Novel Role of Numb as A Regulator of Pro-inflammatory Cytokine Production in Macrophages in Response to Toll-like Receptor 4

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Patipark Kueanjinda ◽  
Sittiruk Roytrakul ◽  
Tanapat Palaga
Keyword(s):  
Notch Signaling ◽  
P38 Mapk ◽  
Inflammatory Responses ◽  
Notch Signaling Pathway ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Murine Bone Marrow

Abstract Activation of macrophages triggers the release of pro-inflammatory cytokines leading to inflammation. Numb is a negative regulator of Notch signaling, but the role of Numb in macrophages is not fully understood. In this study, the role of Numb as a regulator of inflammatory responses in macrophages was investigated. Murine bone marrow-derived macrophages, in which expression of Numb was silenced, secreted significantly less TNFα, IL-6 and IL-12 and more IL-10 upon activation by lipopolysaccharide (LPS), a ligand for Toll-like receptor 4 (TLR4), despite increased Notch signaling. The Tnfα mRNA levels both in Numb-deficient and wild-type macrophages were not significantly different, unlike those of Il6 and Il12-p40. In Numb-deficient macrophages, the Tnfα mRNAs were degraded at faster rate, compared to those in control macrophages. Activation of p38 MAPK and NF-κΒ p65 were compromised in activated Numb deficient macrophages. Numb was found to interact with the E3 ubiquitin ligase, Itch, which reportedly regulates p38 MAPK. In addition, blocking the Notch signaling pathway in activated, Numb-deficient macrophages did not further reduce TNFα levels, suggesting a Notch-independent role for Numb. A proteomics approach revealed a novel funciton for Numb in regulating complex signaling cascades downstream of TLRs, partially involving Akt/NF-κB p65/p38 MAPK in macrophages.

scholarly journals MiRNA-194 Regulates Palmitic Acid-Induced Toll-Like Receptor 4 Inflammatory Responses in THP-1 Cells

Nutrients ◽  
2015 ◽  
Vol 7 (5) ◽  
pp. 3483-3496 ◽  
Author(s):  
Huiqun Tian ◽  
Chaoqi Liu ◽  
Xiaohua Zou ◽  
Wei Wu ◽  
Changcheng Zhang ◽  
...  
Keyword(s):  
Palmitic Acid ◽  
Inflammatory Responses ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

scholarly journals Toll-Like Receptor 4 Promotes NO Synthesis by Upregulating GCHI Expression under Oxidative Stress Conditions in Sheep Monocytes/Macrophages

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Shoulong Deng ◽  
Kun Yu ◽  
Baolu Zhang ◽  
Yuchang Yao ◽  
Zhixian Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Inflammatory Responses ◽  
Gram Negative Bacteria ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Gram Negative ◽  
Transgenic Sheep ◽  
And Oxidative Stress

Many groups of Gram-negative bacteria cause diseases that are harmful to sheep. Toll-like receptor 4 (TLR4), which is critical for detecting Gram-negative bacteria by the innate immune system, is activated by lipopolysaccharide (LPS) to initiate inflammatory responses and oxidative stress. Oxidation intermediates are essential activators of oxidative stress, as low levels of free radicals form a stressful oxidative environment that can clear invading pathogens. NO is an oxidation intermediate and its generation is regulated by nitric oxide synthase (iNOS). Guanosine triphosphate cyclohydrolase (GCHI) is the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, which is essential for the production of inducible iNOS. Previously, we made vectors to overexpress the sheepTLR4gene. Herein, first generation (G1) of transgenic sheep was stimulated with LPSin vivoandin vitro, and oxidative stress and GCHI expression were investigated. Oxidative injury caused by TLR4 overexpression was tightly regulated in tissues. However, the transgenic (Tg) group still secreted nitric oxide (NO) when an iNOS inhibitor was added. Furthermore, GCHI expression remained upregulated in both serum and monocytes/macrophages. Thus, overexpression of TLR4 in transgenic sheep might accelerate the clearance of invading microbes through NO generation following LPS stimulation. Additionally, TLR4 overexpression also enhances GCHI activation.

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