TNFα-INDUCED SUPPRESSION OF PMN APOPTOSIS IS MEDIATED THROUGH INTERLEUKIN-8 PRODUCTION

Dunican, Annmarie L.; Leuenroth, Stephanie J.; Grutkoski, Patricia S.; Ayala, Alfred; Simms, Henry S.

doi:10.1097/00024382-200014030-00007

Cited by 93 publications

(73 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An example is TNF-a, a pro-inflammatory cytokine whose levels are consistently elevated in the BAL fluid of ALI patients. It has been shown to have a biphasic effect on the rate of PMN apoptosis, with long-term suppression being mediated through the antiapoptotic chemokine IL-8 [108]. Furthermore, TNF-a has been implicated in endothelial cell apoptosis and consequent barrier dysfunction, leading to hyperpermeability [109].…”

Section: Apoptosismentioning

confidence: 99%

Ventilator-associated lung injury: a search for better therapeutic targets

Oeckler¹,

Hubmayr²

2007

European Respiratory Journal

View full text Add to dashboard Cite

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a continuum of injury that may arise from a number of primary insults.Localised injury may progress due to trauma from mechanical ventilation, a finding that has led to intense debate in the clinical and experimental literature over optimal ventilator management. The implementation of low tidal volume strategies has led to an improvement in outcomes; however, mortality remains unacceptably high.In the current review, ventilator-associated lung injury is examined, as it relates to the pathophysiological changes beyond direct airway trauma in ALI and ARDS, and an attempt is made to provide a historical perspective to outline potential current and future pitfalls in the use of surrogate end-points and the discovery of potential biomarkers. The systemic responses that lead to multi-organ dysfunction, the leading causes of morbidity and mortality in ALI and ARDS, are caused by pro-inflammatory signalling cascades and the activation of such diverse mediators as reactive oxygen species, immune response elements, apoptotic constituents and coagulation proteins.These areas are examined, including key mediators, and possible future areas of interest are discussed, including the potential of an ''acute lung injury chip'' to integrate measured surrogate biomarkers with real-time clinical information to improve patient outcomes.

show abstract

Section: Apoptosismentioning

confidence: 99%

Ventilator-associated lung injury: a search for better therapeutic targets

Oeckler¹,

Hubmayr²

2007

European Respiratory Journal

View full text Add to dashboard Cite

show abstract

“…The increased survival of neutrophils may contribute to the pathophysiology of these inflammatory diseases through excessive release of toxic mediators, resulting in host tissue damage and organ dysfunction. Tumor necrosis factor (TNF)-␣ and other proinflammatory cytokines have been implicated as endogenous mediators responsible for the modulation of neutrophil apoptosis during inflammation (10,12,14,18,22,23,27,31,34,37,39,42,54).…”

mentioning

confidence: 99%

“…TNF-␣ is a unique proinflammatory cytokine whose signaling pathways are linked to both antiapoptotic and proapoptotic responses in neutrophils (3,10,12,23,39,42,54). Neutrophils possess two TNF-␣ receptors, a 55-60 kDa (p60TNFR) and a 75-80 kDa (p80TNFR), and both antiapoptotic and proapoptotic signaling pathways are regulated principally by the p60TNFR (4,33,49).…”

mentioning

confidence: 99%

See 1 more Smart Citation

A role for PKC-δ and PI 3-kinase in TNF-α-mediated antiapoptotic signaling in the human neutrophil

Kilpatrick

Lee

Haines

et al. 2002

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

The proinflammatory cytokine tumor necrosis factor (TNF)-α has been implicated in the attenuation of neutrophil spontaneous apoptosis during sepsis. Antiapoptotic signaling is principally mediated through the p60TNF receptor (p60TNFR). In neutrophils, TNF-α is an incomplete secretagogue and requires input from a ligated integrin(s) for neutrophil activation. In adherent neutrophils, TNF-α triggers association of both protein kinase C (PKC)-δ and phosphatidylinositol (PI) 3-kinase with the p60TNFR. In this study, a role for PKC-δ and PI 3-kinase in TNF-α-mediated antiapoptotic signaling was examined. TNF-α inhibited spontaneous apoptosis in fibronectin-adherent neutrophils, and this antiapoptotic signaling was blocked by the PKC-δ inhibitor rottlerin, but not by an inhibitor of Ca2+-dependent PKC isotypes, Go-6976. Inhibition of PI 3-kinase by LY-294002 also inhibited TNF-α-mediated antiapoptotic signaling. Cycloheximide blocked TNF-α-mediated antiapoptotic signaling, suggesting protein synthesis is required. Inhibition of either PKC-δ or PI 3-kinase attenuated TNF-α-mediated activation of the antiapoptotic transcription factor NFκB. Thus both PKC-δ and PI 3-kinase have essential roles in TNF-α-mediated antiapoptotic signaling in adherent neutrophils.

show abstract

“…Thus, the typical half-life of an unstimulated PMN, before morphologic changes and its removal from circulation, is 6-12 hrs (179). Interestingly, if PMNs from healthy volunteers are stimulated in this naive state by inflammatory agents (e.g., LPS, TNF, IL-8, IL-6, IL-1, granulocyte-macrophage-colony-stimulating factor), the onset of apoptosis can be delayed (179,183,184) (Fig. 1A).…”

Section: Apoptotic Processes Utilized To Resolve Immune Response In Tmentioning

confidence: 99%

Mechanisms of immune resolution

Ayala

Chung

Grutkoski

et al. 2003

Critical Care Medicine

Self Cite

View full text Add to dashboard Cite

Initially after injury, the innate/proinflammatory and some aspects of the acquired immune response are up-regulated to maintain a defense against foreign pathogens, clear tissue debris present at the wound site, and orchestrate aspects of tissue remodeling, cell proliferation and angiogenic process, associated with the wound response. However, for proper wound healing to progress, this initial inflammatory response has to be regulated or shut down so as to allow for the reestablishment of matrix, recellularization, and tissue remodeling. Inability to properly resolve the extent of innate/ acquired response at a site of injury can lead to poor wound healing, immune suppression, and recurrent infectious episodes. This review attempts to summarize information on regulatory mechanisms that are thought to be involved in controlling/resolving innate or acquired immune responses so as to provide a framework for use in thinking about the impact these processes and their manipulation may have on wound healing and its potential management.

show abstract

TNFα-INDUCED SUPPRESSION OF PMN APOPTOSIS IS MEDIATED THROUGH INTERLEUKIN-8 PRODUCTION

Cited by 93 publications

References 0 publications

Ventilator-associated lung injury: a search for better therapeutic targets

Ventilator-associated lung injury: a search for better therapeutic targets

A role for PKC-δ and PI 3-kinase in TNF-α-mediated antiapoptotic signaling in the human neutrophil

Mechanisms of immune resolution

Contact Info

Product

Resources

About