Divergent Effects of Neutrophils on Fas-Induced Pulmonary Inflammation, Apoptosis, and Lung Damage

Bruns, Bastian; Hönle, Theresia; Kellermann, Philipp; Ayala, Alfred; Perl, Mario

doi:10.1097/shk.0000000000000685

Cited by 8 publications

(3 citation statements)

References 169 publications

(236 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a blunt chest trauma model, the intrapulmonary inflammatory reaction was characterized by an excessive influx of proinflammatory chemokines and cytokines including IL-6, as well as with an activation and infiltration with inflammatory neutrophils. This in turn contributed significantly to the injury of epithelial cells with subsequent capillary breakdown and microcirculatory disturbances [42][43][44][45][46] . Other models including chest trauma have confirmed among others the pathomechanistic importance of the proinflammatory mediators IL-6 and also CXCL1 for the development of lung damage 40,41,47,48 .…”

Section: Discussionmentioning

confidence: 99%

Different experimental multiple trauma models induce comparable inflammation and organ injury

Relja

Yang

Bundkirchen

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Multiple injuries appear to be a decisive factor for experimental polytrauma. Therefore, our aim was to compare the inflammatory response and organ damage of five different monotrauma with three multiple trauma models. For this, mice were randomly assigned to 10 groups: Healthy control (Ctrl), Sham, hemorrhagic shock (HS), thoracic trauma (TxT), osteotomy with external fixation (Fx), bilateral soft tissue trauma (bsTT) or laparotomy (Lap); polytrauma I (PT I, TxT + HS + Fx), PT II (TxT + HS + Fx + Lap) and one multi-trauma group (MT, TxT + HS + bsTT + Lap). The inflammatory response and organ damage were quantified at 6 h by analyses of IL-6, IL-1β, IL-10, CXCL1, SAA1, HMGB1 and organ injury. Systemic IL-6 increased in all mono and multiple trauma groups, while CXCL1 increased only in HS, PT I, PT II and MT vs. control. Local inflammatory response was most prominent in HS, PT I, PT II and MT in the liver. Infiltration of inflammatory cells into lung and liver was significant in all multiple trauma groups vs. controls. Hepatic and pulmonary injury was prominent in HS, PT I, PT II and MT groups. These experimental multiple trauma models closely mimic the early post-traumatic inflammatory response in human. Though, the choice of read-out parameters is very important for therapeutic immune modulatory approaches.

show abstract

Section: Discussionmentioning

confidence: 99%

Different experimental multiple trauma models induce comparable inflammation and organ injury

Relja

Yang

Bundkirchen

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…activation of p38 and JnK is considered as a pro-apoptotic signal, while activation of erK1/2 is considered a pro-survival signal (17). The p38MaPK signaling pathway is involved in the functional response of macrophages and neutrophils, including adhesion and apoptosis (41,42), which is implicated in a variety of cardiovascular diseases (43). it has also been shown to regulate a variety of cellular biological events including cell migration, proliferation and differentiation (44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

N‑acetyl cysteine inhibits lipopolysaccharide‑induced apoptosis of human umbilical vein endothelial cells via the p38MAPK signaling pathway

et al. 2019

View full text Add to dashboard Cite

lipopolysaccharide (lPS) can regulate the expression of apoptotic factors, including caspase-3, Bcl-2 and Bcl-2-associated X protein (Bax). nitric oxide (no) plays an important role in apoptosis. n-acetyl cysteine (nac) has been shown to exhibit antioxidant effects in vitro. However, the effects of nac on lPS-induced apoptosis of human umbilical vein endothelial cells (HuVecs) and the associated mechanisms are not well characterized. The present study explored the effect of nac on lPS-induced apoptosis of HuVecs and determined the participation of the p38 mitogen-activated protein kinase (MaPK) pathway in the process of apoptosis. cell viability was assessed using the cell counting Kit-8 (ccK-8) assay. The expression of caspase-3, Bax, Bcl-2, phosphorylated (p)-p38MaPK/total (t-)p38MaPK and p-endothelial e nitric oxide synthase (enoS)/t-enoS proteins were determined by western blotting. The expression levels of caspase-3, Bax and Bcl-2 mrna were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The rate of apoptosis was determined using flow cytometry. an no detection kit (nitric reductase method) was used to determine no concentration. The results of ccK-8 and flow cytometric analyses showed that pretreatment of HuVecs with nac or p38MaPK inhibitor (SB203580) attenuated lPS-induced decrease in cell viability and increase in cell apoptosis. rT-qPcr and western blotting showed that lPS promoted caspase-3 and Bax expression, but inhibited that of Bcl-2 in HuVecs; however, these effects were attenuated by pretreatment with nac or SB203580. lPS stimulation significantly enhanced the expression of p-p38MAPK protein and reduced the expression of p-enoS protein; however, these effects were attenuated by pretreatment with nac or SB203580. nac pretreatment attenuated lPS-induced inhibition of no synthesis, which was consistent with the effects of SB203580. The results demonstrated that nac pretreatment alleviated lPS-induced apoptosis and inhibition of no production in HuVecs. Furthermore, these effects were proposed to be mediated via the p38MaPK signaling pathway.

show abstract

“…(13) show in their elegantly-conducted study that neutrophils are a necessary component of Fas-induced lung injury in neutrophil-reduced mice. Pulmonary Fas activation is an important step in the pathogenesis of ALI and ARDS, but it was unknown if it relied on the migration of activated PMNs into the lung.…”

mentioning

confidence: 99%

What's New in Shock, February 2017?

Auger

Jeschke²

2017

Shock

View full text Add to dashboard Cite

Divergent Effects of Neutrophils on Fas-Induced Pulmonary Inflammation, Apoptosis, and Lung Damage

Cited by 8 publications

References 169 publications

Different experimental multiple trauma models induce comparable inflammation and organ injury

Different experimental multiple trauma models induce comparable inflammation and organ injury

N‑acetyl cysteine inhibits lipopolysaccharide‑induced apoptosis of human umbilical vein endothelial cells via the p38MAPK signaling pathway

What's New in Shock, February 2017?

Contact Info

Product

Resources

About