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2-Chlorofatty Acids Function as New Lipid Mediators in Neutrophil Extracellular Trap Formation and Accelerate Their Own Clearance by Inducing PPAR-alpha Activity
Başlık:
2-Chlorofatty Acids Function as New Lipid Mediators in Neutrophil Extracellular Trap Formation and Accelerate Their Own Clearance by Inducing PPAR-alpha Activity
Yazar:
Palladino, Elisa N. D., author.
ISBN:
9780438127876
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (121 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: David A. Ford Committee members: Ángel Baldán; Jane McHowat.
Özet:
Neutrophils represent the first line of defense as they are the first to be recruited to the site of inflammation. Their role in inflammation is fundamental and complex. Because of their nonspecific action they are often implicated in the degeneration of pathological conditions where the inflammatory component becomes overwhelming. Recently, a new active form of death was described in neutrophils, called NETosis, which is characterized by the loss of nuclear and granule membrane, leading to the blending of granule and nuclear content. This results in chromatin degradation and de-condensation. Once the plasma membrane breaks, a net structure made primarily of DNA strands, decorated with modified histones and granule proteins, is released in the extracellular space, forming neutrophils extracellular traps (NETs). NETs are capable of trapping, disarming and killing bacteria, representing a powerful tool against infections. However, NETs have also been implicated in the aggravation of several pathological conditions, such as thrombosis, sepsis and autoimmune disease. This is why it is imperative to know more about this complicated phenomenon. Previous studies demonstrated the importance of myeloperoxidase (MPO) and NADPH oxidase in NETosis. Nonetheless, the trigger that initiates this complex pathway is yet to be determined. Here we test the role of 2-chlorofatty acids (2-ClFAs), an MPO-derived inflammation product, in NETosis. Our results indicated that 2-ClFAs function as lipid mediators of NETosis, capable of triggering the process independently of neutrophil activation. This led to new insights that offer new potential targets for drug development and aimed therapies. In this same research study, we investigated the clearance of 2-ClFAs, depicting in more detail the regulatory process that controls 2-ClFA catabolism. We found that peroxisome proliferator-activated receptor-alpha (PPAR-alpha) controls the expression of the machinery responsible for 2-ClFA catabolism in the liver. The agonist-mediated enhancement of PPAR-alpha activity significantly improved 2-ClFA clearance in vivo, indicating a practical preventative approach to lower 2-ClFA level during inflammation.
Notlar:
School code: 0193
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(693764.1) | 693764-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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