Signaling mechanisms in Streptococcal M1 proteininduced inflammation and injury in the lung

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

Bibtex

@phdthesis{64c8150d815f471882924be0d0085e27,
title = "Signaling mechanisms in Streptococcal M1 proteininduced inflammation and injury in the lung",
abstract = "Streptococcus pyogenes of the M1 serotype is frequently associated with severe streptococcal infections. Acute lung injury is recognized as a key component in the pathophysiology of streptococcal M1 proteininduced inflammation. Numerous reports have demonstrated that excessive infiltration of neutrophils is a rate-limiting step in septic lung damage. We observed that targeting neutrophil functions appeared more relevant than inhibiting platelet activation in severe infections triggered by streptococcal M1 protein. In study II, it was shown that simvastatin was a powerful inhibitor of neutrophil infiltration in acute lung damage triggered by streptococcal M1 protein. The inhibitory effect of simvastatin on M1 protein-induced neutrophil recruitment appeared related to reduced pulmonary generation of CXC chemokines. Following the mevalonate signaling pathway, checking downstream effectors, both Rho/Rho Kinase and p38 MAPK signaling pathway played critical roles in M1 protein-induced lung recruitment of neutrophils via formation of CXC chemokines and Mac-1 expression. In addition, our findings also suggested that farnesyltransferase was a potent regulator of CXC chemokine formation in alveolar macrophages and that inhibition of farnesyltransferase not only reduces neutrophil recruitment but also attenuates acute lung injury provoked by streptococcal M1 protein. Thus, these new data may provide a basis for the development of more specific and effective treatment of patients with STSS.",
author = "Songen Zhang",
note = "Defence details Date: 2012-11-30 Time: 13:00 Place: CRC Aula, Entrance 72, Sk{\aa}ne University Hospital, Malm{\"o} External reviewer(s) Name: Sund, Malin Title: [unknown] Affiliation: Department of Surgical and Perioperative Sciences,University of Ume{\aa}, Sweden ---",
year = "2012",
language = "English",
isbn = "978-91-87189-67-8",
series = "Lund University Faculty of Medicine Doctoral Dissertation Series ",
publisher = "Surgery Research Unit, Clinical Science, Malm{\"o}",
school = "Surgery",

}