Novel Role of IL (Interleukin)-1β in Neutrophil Extracellular Trap Formation and Abdominal Aortic Aneurysms

Meher, Akshaya K.; Spinosa, Michael; Davis, John Staige; Pope, Nicolas H.; Laubach, Victor E.; Su, Gang; Serbulea, Vlad; Leitinger, Norbert; Ailawadi, Gorav; Upchurch, Gilbert R.

doi:10.1161/atvbaha.117.309897

Cited by 186 publications

(182 citation statements)

References 29 publications

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“…The triggers of NETosis in COVID-19 are potentially myriad and will require further investigation. Possibilities include virus-damaged epithelial cells (13,29), activated platelets (30,31), activated endothelial cells (32), and inflammatory cytokines such as IL-1β (19,33), IL-8 (34,35), granulocyte colony stimulating factor (36,37), and likely others (17).…”

Section: Discussionmentioning

confidence: 99%

“…Although it has yet to be assessed whether NETs contribute to the inflammatory storm that leads to respiratory failure in many COVID-19 patients, there is emerging evidence to implicate inflammatory cytokines such as interleukin (IL)-1β and IL-6 in the COVID-19 milieu (17). Not surprisingly, NETs are intimately intertwined with both cytokines, and especially IL-1β, in many pulmonary and cardiovascular diseases (8,(18)(19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

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Neutrophil extracellular traps in COVID-19

Zuo¹,

Yalavarthi²,

Shi³

et al. 2020

JCI Insight

1,228

1,386

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neutrophil extracellular traps in COVID-19

Zuo¹,

Yalavarthi²,

Shi³

et al. 2020

JCI Insight

1,228

1,386

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“…Moreover, cytokine storms lead to acute lung injury, ARDS, and death (Channappanavar and Perlman, 2017; Chousterman et al, 2017). It is especially noteworthy that NETs can induce macrophages to secrete IL1β and that IL1β enhances NET formation in various diseases, including aortic aneurysms and atherosclerosis (Kahlenberg et al, 2013; Meher et al, 2018; Sil et al, 2017; Warnatsch et al, 2015). Together, these data suggest that under conditions in which the normal signals to dampen inflammation are lost, such as during a cytokine storm, a signaling loop between macrophages and neutrophils can lead to uncontrollable, progressive inflammation.…”

Section: Nets and The Cytokine Stormmentioning

confidence: 99%

Targeting potential drivers of COVID-19: Neutrophil extracellular traps

Barnes

Adrover

Baxter-Stoltzfus

et al. 2020

Journal of Experimental Medicine

1,364

1,462

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Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10–15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils—the ability to form neutrophil extracellular traps (NETs)—may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.

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“…In addition, we observed that NETs were predominantly located in the subepithelial layer of nasal polyp tissue (Figure A). Typical NETs were extracellular cloud structures that stained positive for DNA and MPO (Figure B), which was further confirmed by additional IF staining positive for DNA, MPO, and citrullinated histone H3 (Cit‐H3), a marker for NET formation (Figure ). As expected, the number of NETs was highly correlated with that of neutrophil in nasal tissues (Figure F), and NET count and NETs% were significantly increased in Neu‐NP compared with Non‐Neu‐NP (Figure G‐H).…”

Section: Resultsmentioning

confidence: 65%

LL‐37 promotes neutrophil extracellular trap formation in chronic rhinosinusitis with nasal polyps

Cao

Chen

Sun

et al. 2019

Clin Experimental Allergy

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Background Neutrophil accumulation has been observed in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the functions of neutrophils are poorly understood. Neutrophils produce neutrophil extracellular traps (NETs), which are involved in a variety of chronic inflammatory pathologies. LL‐37 is the only member of the cathelicidin family in human. Objective Our aims were to examine the presence of NETs in CRSwNP and to investigate the regulatory effect of LL‐37 on NET formation. Methods Nasal polyp tissues were investigated for the presence of NETs by using immunofluorescent (IF) staining. The expression and distribution of LL‐37 were examined by using quantitative RT‐PCR, ELISA, IF, and immunohistochemistry. Purified peripheral neutrophils were stimulated with LL‐37 and stained with IF to identify NETs. NETs% was defined as percentage of NET‐generating neutrophils to the total number of neutrophils. Results Neutrophil extracellular traps were located in the subepithelial layer of nasal polyps and control tissues. Nasal polyps had higher NETs% compared with that of controls (23.01% ± 3.43% vs 4.52% ± 1.33%, P < 0.0001). NET count was also increased in nasal polyps. NET count correlated with neutrophil count (r = 0.908, P < 0.001). LL‐37 protein and mRNA levels were upregulated in nasal polyps. LL‐37 was distributed in the epithelial and subepithelial layer and mainly expressed by neutrophils. Moreover, LL‐37 promoted peripheral neutrophils to form NETs in a dose‐dependent manner ex vivo. Interestingly, dexamethasone did not inhibit the effect of LL‐37 on inducing NET formation. Furthermore, peripheral neutrophils from CRSwNP patients were more susceptible to LL‐37‐mediated NET formation, compared with neutrophils derived from control subjects. In addition, NETs released LL‐37 in vivo and ex vivo. Conclusion Neutrophil extracellular traps are significantly increased in nasal polyps and LL‐37 induces NET formation in CRSwNP patients. These findings indicate that NETs may contribute to the pathogenesis of neutrophilic inflammation in CRSwNP.

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Novel Role of IL (Interleukin)-1β in Neutrophil Extracellular Trap Formation and Abdominal Aortic Aneurysms

Abstract: Altogether, the results suggest a dominant role of IL-1β-induced NETosis in AAA formation.

Cited by 186 publications

References 29 publications

Neutrophil extracellular traps in COVID-19

Neutrophil extracellular traps in COVID-19

Targeting potential drivers of COVID-19: Neutrophil extracellular traps

LL‐37 promotes neutrophil extracellular trap formation in chronic rhinosinusitis with nasal polyps

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