119 Toll-Like Receptor-4 Agonist Monophosphoryl Lipid A Attenuates Severity of Acute Lung Injury and Hemodynamic Changes in an Ovine Model of Cutaneous Burn and Pneumonia Sepsis

2018 ◽  
Vol 39 (suppl_1) ◽  
pp. S65-S66
Author(s):  
S Fukuda ◽  
S Michael ◽  
K Ihara ◽  
R A Cox ◽  
D N Herndon ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lipid A ◽  
Toll Like Receptor ◽  
Ovine Model ◽  
Hemodynamic Changes ◽  
Toll Like Receptor 4 ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

scholarly journals A Translatable Subunit Nanovaccine for COVID-19

2020 ◽  
Author(s):  
Lixin Liu ◽  
Zhijia Liu ◽  
Haolin Chen ◽  
Hong Liu ◽  
Qiang Gao ◽  
...  
Keyword(s):  
Lipid A ◽  
Vero Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Cd8 Cells ◽  
Humoral Immune ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Cell Immunity ◽  
Iga Antibody

In order to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in the world, we formulate S1 subunit of the virus with two types of adjuvants, amphiphilic adjuvant monophosphoryl lipid A (MPLA) for Toll-like receptor 4 (TLR4) and CpG ODN for TLR9, into cationic multifunctional liposomes to produce a potent, safer, and translatable nanovaccine. The results show that the nanovaccine can efficiently elicit humoral immune response in mice. The sera from the vaccinated mice significantly inhibit SARS-CoV-2 to infect Vero cells. Moreover, relatively to the free S1 with traditional Alum adjuvant, the nanovaccine can elicit strong T cell immunity by activating both CD4+ and CD8+ cells, which may play critical roles in eliminating viral load in patients. Most importantly, the nanovaccine can elicit strong IgA antibody, providing potential mucosal protection to host. Altogether, this study offers a translatable design for a potent subunit SARS-CoV-2 nanovaccine.

scholarly journals The Toll-Like Receptor 4 Agonist Monophosphoryl Lipid A Augments Innate Host Resistance to Systemic Bacterial Infection

2011 ◽  
Vol 79 (9) ◽  
pp. 3576-3587 ◽  
Author(s):  
Christopher D. Romero ◽  
Tushar K. Varma ◽  
Jason B. Hobbs ◽  
Aimee Reyes ◽  
Brandon Driver ◽  
...  
Keyword(s):  
Lipid A ◽  
Cytokine Production ◽  
Myeloid Cells ◽  
Innate Immune ◽  
Bacterial Clearance ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Systemic Dissemination

ABSTRACTMonophosphoryl lipid A (MPLA) is a Toll-like receptor 4 (TLR4) agonist that is currently used as a vaccine adjuvant in humans. In this study, we evaluated the effect of MPLA treatment on the innate immune response to systemic bacterial infections in mice. Mice treated with MPLA after burn injury showed improved survival and less local and systemic dissemination of bacteria in a model ofPseudomonas aeruginosaburn wound infection. Prophylactic treatment with MPLA significantly enhanced bacterial clearance at the site of infection and reduced systemic dissemination of bacteria despite causing attenuation of proinflammatory cytokine production during acute intra-abdominal infection caused by cecal ligation and puncture. Administration of MPLA at 1 h after CLP also improved bacterial clearance but did not alter cytokine production. MPLA treatment increased the numbers of granulocytes, double-positive myeloid cells, and macrophages at sites of infection and increased the percentage and total numbers of myeloid cells mediating phagocytosis of bacteria. Depletion of Ly6G+neutrophils, but not macrophages, eliminated the ability of MPLA treatment to improve bacterial clearance. The immunomodulatory effects of MPLA were absent in TLR4-deficient mice. In conclusion, these studies show that MPLA treatment significantly augments the innate immune response to bacterial infection by enhancing bacterial clearance despite the attenuation of proinflammatory cytokine production. The enhanced bacterial clearance is mediated, in part, by increased numbers of myeloid cells with effective phagocytic functions at sites of infection and is TLR4 dependent.

scholarly journals A Translatable Subunit Nanovaccine for COVID-19

2020 ◽  
Author(s):  
Lixin Liu ◽  
Zhijia Liu ◽  
Haolin Chen ◽  
Hong Liu ◽  
Qiang Gao ◽  
...  
Keyword(s):  
Lipid A ◽  
Vero Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Cd8 Cells ◽  
Humoral Immune ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Cell Immunity ◽  
Iga Antibody

In order to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in the world, we formulate S1 subunit of the virus with two types of adjuvants, amphiphilic adjuvant monophosphoryl lipid A (MPLA) for Toll-like receptor 4 (TLR4) and CpG ODN for TLR9, into cationic multifunctional liposomes to produce a potent, safer, and translatable nanovaccine. The results show that the nanovaccine can efficiently elicit humoral immune response in mice. The sera from the vaccinated mice significantly inhibit SARS-CoV-2 to infect Vero cells. Moreover, relatively to the free S1 with traditional Alum adjuvant, the nanovaccine can elicit strong T cell immunity by activating both CD4+ and CD8+ cells, which may play critical roles in eliminating viral load in patients. Most importantly, the nanovaccine can elicit strong IgA antibody, providing potential mucosal protection to host. Altogether, this study offers a translatable design for a potent subunit SARS-CoV-2 nanovaccine.

Chelidonine Attenuates Sepsis-Induced Acute Lung Injury via Suppressing Toll-like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-॔B Signaling Pathway in Newborn Mice

2020 ◽  
Vol 19 (1) ◽  
pp. 120-126
Author(s):  
Ayinuerguli Adili ◽  
Adilijiang Kari ◽  
Chuanlong Song ◽  
Abulaiti Abuduhaer
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Myeloid Differentiation ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Inflammatory Infiltration ◽  
Newborn Mice ◽  
Myeloid Differentiation Factor

We have examined the mechanism underlying amelioration of sepsis-induced acute lung injury by chelidonine in newborn mice. To this end, a sepsis model was established using cecal ligation and puncture in newborn mice. The sepsis-induced acute lung injury was associated with an increased inflammatory infiltration and pulmonary congestion, as well as abnormal alveolar morphology. The lung injury-associated increased tumor necrosis factor-α and interleukin-1β in bronchoalveolar lavage fluid and lung, the markers of inflammatory infiltration and pulmonary congestion, diminished by chelidonine treatment. Chelidonine administration also downregulated protein levels of toll-like receptor 4, myeloid differentiation factor 88, phosphorylated nuclear factor-kappa B, and nuclear factor-kappa B that are elevated in response to sepsis. In conclusion, chelidonine provides a potential therapeutic strategy for newborn mice with acute lung injury.

Juglone Attenuates Sepsis-Induced Acute Lung Injury via Suppression of the TLR4/Nf-κb Pathway

2020 ◽  
Vol 18 (2) ◽  
pp. 201-206
Author(s):  
Qiu Nan ◽  
Xu Xinmei ◽  
He Yingying ◽  
Fan Chengfen
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Cecal Ligation ◽  
Myeloperoxidase Activity ◽  
Nuclear Factor ◽  
Cecal Ligation And Puncture ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Nuclear Factor Kappa

Sepsis, with high mortality, induces deleterious organ dysfunction and acute lung injury. Natural compounds show protective effect against sepsis-induced acute lung injury. Juglone, a natural naphthoquinone, demonstrates pharmacological actions as a pro-apoptotic substrate in tumor treatment and anti-inflammation substrate in organ injury. In this study, the influence of juglone on sepsis-induced acute lung injury was investigated. First, a septic mice model was established via cecal ligation and puncture, and then verified via histopathological analysis of lung tissues, the wet/dry mass ratio and myeloperoxidase activity was determined. Cecal ligation and puncture could induce acute lung injury in septic mice, as demonstrated by alveolar damage and increase of wet/dry mass ratio and myeloperoxidase activity. However, intragastric administration juglone attenuated cecal ligation and puncture-induced acute lung injury. Secondly, cecal ligation and puncture-induced increase of inflammatory cells in bronchoalveolar lavage fluid was also alleviated by the administration of juglone. Similarly, the protective effect of juglone against cecal ligation and puncture-induced acute lung injury was accompanied by a reduction of pro-inflammatory factor secretion in bronchoalveolar lavage fluid and lung tissues. Cecal ligation and puncture could activate toll-like receptor 4/nuclear factor-kappa B signaling pathway, and administration of juglone suppressed toll-like receptor 4/nuclear factor-kappa B activation. In conclusion, juglone attenuated cecal ligation and puncture-induced lung damage and inflammatory response through inactivation of toll-like receptor 4/nuclear factor-kappa B, suggesting a potential therapeutic strategy in the treatment of sepsis-induced acute lung injury.

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