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Method for modulating inflammasome activity and inflammation in the lung

A technology of inflammasome and lung inflammation, applied in the field of immunology and medicine, can solve the problems of ignorance of pathological mechanism, unclear pathological mechanism of inflammasome signal transduction, lack, etc.

Pending Publication Date: 2019-11-15
UNIV OF MIAMI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it remains unclear whether EV-mediated inflammasome signaling may contribute to the pathology of TBI-induced ALI
Furthermore, it is not known whether the pathological mechanism of TBI-induced ALI is common to other conditions that produce pneumonia
Additionally, there is a lack of FDA-approved drugs for the treatment of pneumonia

Method used

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  • Method for modulating inflammasome activity and inflammation in the lung
  • Method for modulating inflammasome activity and inflammation in the lung
  • Method for modulating inflammasome activity and inflammation in the lung

Examples

Experimental program
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Effect test

Embodiment 1

[0089] Example 1: The role and neutralization of EV-mediated inflammasome signaling in ALI after TBI

[0090] Pulmonary dysfunction often presents as a complication of severe traumatic brain injury (1). Approximately 20%-25% of TBI subjects develop acute lung injury (ALI) (2), but the mechanisms mediating TBI-induced ALI pathology remain poorly defined. Previous literature supports the notion that pulmonary dysfunction after TBI is due to cardiopulmonary dysfunction due to sympathetic responses to elevated intracranial pressure (42). However, recent studies have shown that systemic inflammatory responses also play a key role in TBI-induced lung injury (43). Specifically, the HMGB1-RAGE ligand-receptor pathway serves as a central transduction mechanism for lung dysfunction after TBI (8). Furthermore, HMGB1 induces AIM2 inflammasome activation (37). Furthermore, previous literature revealed that pathogens secrete EVs carrying DAMPs, such as HMGB1, and trigger inflammation (Bu...

Embodiment 2

[0187] Example 2: Role of EV-mediated inflammasome signaling in ALI after TBI in human patients

[0188] As a follow-up to the experiments on mice in Example 1, the effect of EVs isolated from human TBI patients on inflammasome signaling in human lung endothelial cells was examined.

[0189]In the first experiment, serum-derived EVs were isolated from TBI and control patients using the Total Exosome Isolation Kit (Thermofisher). Lung human microvascular endothelial cells (HMVEC-Lonza) were cultured and spread on 12-well plates. After reaching confluency, isolated EVs (1.94 x 108 particles / ml) from TBI and control patients were delivered to the cells with an incubation period of 4 hours. After incubation, cells were harvested with 200ul of lysis buffer, and cell lysates were used for Western blot analysis.

[0190] In the second experiment, serum-derived EVs were isolated from TBI and control patients using the Total Exosome Isolation Kit (Thermofisher). Lung human microvasc...

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Abstract

The present invention provides compositions and methods for reducing inflammation in the lungs of a mammal that is afflicted by a condition that leads to inflammation in the lungs. The compositions and methods described herein include agents that inhibit inflammasome signaling in the mammal such as antibodies directed against inflammasome components used alone or in combination with extracellularvesicle uptake inhibitor(s).

Description

[0001] This application claims priority to US Provisional Application Serial No. 62 / 440,180, filed December 29, 2016, which is hereby incorporated by reference in its entirety for all purposes. [0002] Statement Regarding Federally Sponsored Research [0003] This invention was made with US Government support under Grant No. 4R42BS086274-02 awarded by the National Institute of Neurological Disorders and Stroke (NINDS). The US Government has certain rights in this invention. [0004] Instructions for electronically submitting text files [0005] The contents of the electronically submitted text file are incorporated herein by reference in their entirety: Copy of Sequence Listing in Computer Readable Format (File Name: UNMI_010_01WO_SeqList_ST25.txt, Date of Record: December 28, 2017, File Size 2 Kbytes ). technical field [0006] The present invention relates generally to the fields of immunology and medicine. More specifically, the present invention relates to methods for...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P29/00
CPCA61P29/00C07K16/18A61K2039/505A61P25/14A61P25/28A61P37/06C07K2317/76A61K31/737A61K38/00A61P11/00A61P25/00C07K2317/24A61K31/727A61K2300/00A61K39/39541A61K39/3955A61K2039/55A61K2039/55522C07K16/24A61P21/00C07K2317/56C07K2317/565C07K2317/21C07K2317/34
Inventor R·基恩D·迪特里希N·克尔S·吴J·P·德里韦罗·瓦卡里
Owner UNIV OF MIAMI
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