Blocking CXCR1/2 contributes to amelioration of lipopolysaccharide‐induced sepsis by downregulating substance P

Wang, Miaoshu; Zhong, Danfeng; Dong, Ping; Song, Yukang

doi:10.1002/jcb.27507

Cited by 7 publications

(7 citation statements)

References 23 publications

(52 reference statements)

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“…Largely in agreement with our findings, miR‐326 activates the NF‐κB signalling pathway through target inhibition of B cell leukaemia/lymphoma 2–related protein A1, by which inflammatory responses and lung injuries of mice with ALI were aggravated 41 . More importantly, function studies have shown that the inactivation of the NF‐κB signalling pathway can reduce oxidative stress to allow improvement of ALI; CXCR1/2 antagonists can ameliorate LPS‐induced ALI in association with sepsis 42,43 . Concordantly, the addition of PDTC, an inhibitor of the NF‐κB signalling pathway, resulted in alleviated lung injuries induced by NET, as observed in mouse models of TRALI in our study.…”

Section: Discussionsupporting

confidence: 89%

“…41 More importantly, function studies have shown that the inactivation of the NF-κB signalling pathway can reduce oxidative stress to allow improvement of ALI; CXCR1/2 antagonists can ameliorate LPS-induced ALI in association with sepsis. 42,43 Concordantly, the addition of PDTC, an inhibitor of the NF-κB signalling pathway, resulted in alleviated lung injuries induced by NET, as observed in mouse models of TRALI in our study.…”

Section: Discussionsupporting

confidence: 78%

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MiR‐144‐induced KLF2 inhibition and NF‐kappaB/CXCR1 activation promote neutrophil extracellular trap–induced transfusion‐related acute lung injury

Liu

et al. 2021

J Cellular Molecular Medi

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 78%

MiR‐144‐induced KLF2 inhibition and NF‐kappaB/CXCR1 activation promote neutrophil extracellular trap–induced transfusion‐related acute lung injury

Liu

et al. 2021

J Cellular Molecular Medi

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“…In this context, antagonists of IL-8 are already used in the treatment of severe inflammatory conditions. However, the data are still limited and partly inconsistent [38-40]. Overall, IL-8 clearly plays an important role during systemic inflammation [6, 9, 10, 41, 42].…”

Section: Introductionmentioning

confidence: 99%

Interleukin 8 Elicits Rapid Physiological Changes in Neutrophils That Are Altered by Inflammatory Conditions

et al. 2021

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A sufficient response of neutrophil granulocytes stimulated by interleukin (IL)-8 is vital during systemic inflammation, for example, in sepsis or severe trauma. Moreover, IL-8 is clinically used as biomarker of inflammatory processes. However, the effects of IL-8 on cellular key regulators of neutrophil properties such as the intracellular pH (pH<sub>i</sub>) in dependence of ion transport proteins and during inflammation remain to be elucidated. Therefore, we investigated in detail the fundamental changes in pH<sub>i</sub>, cellular shape, and chemotactic activity elicited by IL-8. Using flow cytometric methods, we determined that the IL-8-induced cellular activity was largely dependent on specific ion channels and transporters, such as the sodium-proton exchanger 1 (NHE1) and non-NHE1-dependent sodium flux. Exposing neutrophils in vitro to a proinflammatory micromilieu with N-formyl-Met-Leu-Phe, LPS, or IL-8 resulted in a diminished response regarding the increase in cellular size and pH. The detailed kinetics of the reduced reactivity of the neutrophil granulocytes could be illustrated in a near-real-time flow cytometric measurement. Last, the LPS-mediated impairment of the IL-8-induced response in neutrophils was confirmed in a translational, animal-free human whole blood model. Overall, we provide novel mechanistic insights for the interaction of IL-8 with neutrophil granulocytes and report in detail about its alteration during systemic inflammation.

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“…References NF-κB pathway and macrophages release pro-inflammatory cytokines, leading to lung inflammation and injury The expression of CXCR1/2 and p-MLKL is high, and the SP level is high while the VIP level is low. All could be reversed by reparixin, a CXCR antagonist that increased the survival rate mice of mice and improved lung inflammation Wang et al (2018b) hyperoxic acute lung injury (HALI)…”

Section: More Specific Main Content About Necroptosismentioning

confidence: 99%

Necroptosis in Pulmonary Diseases: A New Therapeutic Target

Wang

Zhou

et al. 2021

Front. Pharmacol.

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In the past decades, apoptosis has been the most well-studied regulated cell death (RCD) that has essential functions in tissue homeostasis throughout life. However, a novel form of RCD called necroptosis, which requires receptor-interacting protein kinase-3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL), has recently been receiving increasing scientific attention. The phosphorylation of RIPK3 enables the recruitment and phosphorylation of MLKL, which oligomerizes and translocates to the plasma membranes, ultimately leading to plasma membrane rupture and cell death. Although apoptosis elicits no inflammatory responses, necroptosis triggers inflammation or causes an innate immune response to protect the body through the release of damage-associated molecular patterns (DAMPs). Increasing evidence now suggests that necroptosis is implicated in the pathogenesis of several human diseases such as systemic inflammation, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, neurological diseases, and cancer. This review summarizes the emerging insights of necroptosis and its contribution toward the pathogenesis of lung diseases.

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Blocking CXCR1/2 contributes to amelioration of lipopolysaccharide‐induced sepsis by downregulating substance P

Abstract: The results of this study indicate that blockade of CXCR1/2 may represent a promising therapeutic strategy for the treatment of sepsis-associated ALI through regulation of neuropeptides and necroptosis.

Cited by 7 publications

References 23 publications

MiR‐144‐induced KLF2 inhibition and NF‐kappaB/CXCR1 activation promote neutrophil extracellular trap–induced transfusion‐related acute lung injury

MiR‐144‐induced KLF2 inhibition and NF‐kappaB/CXCR1 activation promote neutrophil extracellular trap–induced transfusion‐related acute lung injury

Interleukin 8 Elicits Rapid Physiological Changes in Neutrophils That Are Altered by Inflammatory Conditions

Necroptosis in Pulmonary Diseases: A New Therapeutic Target

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