Kearney C.J.,Smurfit Institute |
Sheridan C.,Smurfit Institute |
Cullen S.P.,Smurfit Institute |
Cullen S.P.,Trinity College Dublin |
And 7 more authors.
Journal of Biological Chemistry | Year: 2013
Background: IAP antagonists sensitize toward apoptosis induced by TNF and other TNFR family ligands. Results: IAP antagonism exerted effects on spontaneous as well as TNF-induced cytokine and chemokine production. Conclusion: IAPs regulate spontaneous as well as TNF-induced cytokine/chemokine production. Significance: IAP antagonists modulate cytokine production as well as apoptosis, which could influence their utility as adjuncts to chemotherapy.© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
Dillon S.C.,Moyne Institute of Preventive Medicine |
Cameron A.D.S.,Moyne Institute of Preventive Medicine |
Hokamp K.,Smurfit Institute |
Lucchini S.,UK Institute of Food Research |
And 2 more authors.
Molecular Microbiology | Year: 2010
The conjugative IncHI1 plasmid pSfR27 from Shigella flexneri 2a strain 2457T encodes the Sfh protein, a paralogue of the global transcriptional repressor H-NS. Sfh allows pSfR27 to be transmitted to new bacterial hosts with minimal impact on host fitness, providing a 'stealth' function whose molecular mechanism has yet to be determined. The impact of the Sfh protein on the Salmonella enterica serovar Typhimurium transcriptome was assessed and binding sites for Sfh in the Salmonella Typhimurium genome were identified by chromatin immunoprecipitation. Sfh did not bind uniquely to any sites. Instead, it bound to a subset of the larger H-NS regulatory network. Analysis of Sfh binding in the absence of H-NS revealed a greatly expanded population of Sfh binding sites that included the majority of H-NS target genes. Furthermore, the presence of plasmid pSfR27 caused a decrease in H-NS interactions with the S. Typhimurium chromosome, suggesting that the A + T-rich DNA of this large plasmid acts to titrate H-NS, removing it from chromosomal locations. It is proposed that Sfh acts as a molecular backup for H-NS and that it provides its 'stealth' function by replacing H-NS on the chromosome, thus minimizing disturbances to the H-NS-DNA binding pattern in cells that acquire pSfR27. © 2010 Blackwell Publishing Ltd.
Davidovich P.,Saint Petersburg State Polytechnic University |
Kearney C.J.,Smurfit Institute |
Martin S.J.,Dublin Institute of Technology
Biological Chemistry | Year: 2014
Microbial infection and tissue injury are well established as the two major drivers of inflammation. However, although it is widely accepted that necrotic cell death can trigger or potentiate inflammation, precisely how this is achieved still remains relatively obscure. Certain molecules, which have been dubbed 'damage-associated molecular patterns' (DAMPs) or alarmins, are thought to promote inflammation upon release from necrotic cells. However, the precise nature and relative potency of DAMPs, compared to conventional pro-inflammatory cytokines or pathogen-associated molecular patterns (PAMPs), remains unclear. How different modes of cell death impact on the immune system also requires further clarification. Apoptosis has long been regarded as a non-inflammatory or even anti-inflammatory mode of cell death, but recent studies suggest that this is not always the case. Necroptosis is a programmed form of necrosis that is engaged under certain conditions when caspase activation is blocked. Necroptosis is also regarded as a highly pro-inflammatory mode of cell death but there has been little explicit examination of this issue. Here we discuss the inflammatory implications of necrosis, necroptosis and apoptosis and some of the unresolved questions concerning how dead cells influence inflammatory responses. © 2015, WDG. All rights reserved.