Leukotriene B4 receptors play critical roles in house dust mites-induced neutrophilic airway inflammation and IL-17 production

Kwak, Dong Wook; Park, Donghwan; Kim, Jae Hong

doi:10.1016/j.bbrc.2020.11.027

Cited by 7 publications

(10 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, we observed that BLT2 and its ligand 12( S )-HETE played critical roles in asthmatic airway inflammation [ 23 , 24 , 25 , 26 , 27 , 28 ]. Especially, BLT2 was shown to play mediatory roles in the production of IL-17 and IL-1β, eventually contributing to the neutrophilic asthma development in the murine models [ 29 , 30 , 31 ]. However, the mediatory role of BLT2 in G-CSF production in neutrophilic asthma has not been elucidated yet.…”

Section: Introductionmentioning

confidence: 99%

Leukotriene B4 Receptor 2 Mediates the Production of G-CSF That Plays a Critical Role in Steroid-Resistant Neutrophilic Airway Inflammation

2022

Self Cite

View full text Add to dashboard Cite

Granulocyte colony-stimulating factor (G-CSF) has been suggested to be closely associated with neutrophilic asthma pathogenesis. However, little is known about the factors regulating the production of G-CSF in neutrophilic asthma. We previously reported that a leukotriene B4 receptor 2, BLT2, played an important role in neutrophilic airway inflammation. Therefore, in the current study, we investigated whether BLT2 plays a role in the production of G-CSF in lipopolysaccharide/ovalbumin (LPS/OVA)-induced steroid-resistant neutrophilic asthma. The data showed that BLT2 critically mediated G-CSF production, contributing to the progression of neutrophilic airway inflammation. We also observed that 12-lipoxygenase (12-LO), which catalyzes the synthesis of the BLT2 ligand 12(S)-HETE, was also necessary for G-CSF production. Together, these results suggest that the 12-LO-BLT2-linked signaling network is critical for the production of G-CSF, contributing to the development of neutrophilic airway inflammation. Our findings can provide a potential new target for the therapy of severe neutrophilic asthma.

show abstract

Section: Introductionmentioning

confidence: 99%

Leukotriene B4 Receptor 2 Mediates the Production of G-CSF That Plays a Critical Role in Steroid-Resistant Neutrophilic Airway Inflammation

2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, several groups have already reported that the addition of LPS during the HDM sensitization phase caused a neutrophil-dominant lung inflammation [ 30 , 31 ]. Additionally, we previously observed that the addition of LPS during the HDM sensitization phase induced neutrophil-dominant lung airway inflammation [ 6 ]. In that study, we demonstrated that BLT1/2 play critical roles in HDM/LPS-induced neutrophilic airway.…”

Section: Discussionmentioning

confidence: 99%

“…Lung tissue lysates were prepared as described previously [ 6 ]. The lysate samples were heated at 95 °C for 5 min and subjected to SDS-PAGE.…”

Section: Methodsmentioning

confidence: 99%

“…Asthma is an airway inflammatory disease consisting of various phenotypes that are driven by different pathways. Severe asthma is more strongly associated with Th1/Th17 responses and neutrophilic airway inflammation [ 1 , 2 , 3 , 4 , 5 , 6 ]. Approximately 5–20% of asthma patients respond poorly to corticosteroids even at high doses, and no effective treatments are currently available for severe, steroid-resistant asthma [ 3 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, 12( S )-HETE, a 12-LOX product, has been shown to be highly elevated in the serum of the neutrophilic airway inflammation group compared with the healthy control group [ 15 ]. In addition, we previously demonstrated that the LTB 4 receptors BLT1/2 contributed to neutrophilic airway inflammation, especially house dust mite (HDM)/lipopolysaccharide (LPS)-induced neutrophilic airway inflammation and asthmatic exacerbation [ 6 ]. However, it remains to be determined whether BLT1/2 are associated with NLRP3 stimulation and IL-1β synthesis in neutrophilic airway inflammation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Leukotriene B4 Receptors Are Necessary for the Stimulation of NLRP3 Inflammasome and IL-1β Synthesis in Neutrophil-Dominant Asthmatic Airway Inflammation

2021

Self Cite

View full text Add to dashboard Cite

The stimulation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and IL-1β synthesis are associated with chronic respiratory diseases such as neutrophil-dominant severe asthma. Leukotriene B4 (LTB4) is a principal chemoattractant molecule for neutrophil recruitment, and its receptors BLT1 and BLT2 have been suggested to contribute to neutrophil-dominant asthmatic airway inflammation. However, the relationship between BLT1/2 and NLRP3 in neutrophil-dominant asthmatic airway inflammation has not been previously studied. In the present study, we investigated whether BLT1/2 play any roles in stimulating the NLRP3 inflammasome and IL-1βsynthesis. The blockade of BLT1 or BLT2 clearly suppressed the stimulation of the NLRP3 inflammasome and IL-1β synthesis in house dust mite (HDM)/lipopolysaccharide (LPS)-induced neutrophilic airway inflammation. The enzymes 5-lipoxygenase and 12-lipoxygenase, which catalyze the synthesis of BLT1/2 ligands [LTB4, 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), and 12-hydroxyheptadecatreinoic acid (12-HHT)], were also critically associated with the stimulation of NLRP3 and IL-1β synthesis. Together, our results suggest that the 5-/12-LOX-BLT1/2-linked cascade are necessary for the simulation of the NLRP3 inflammasome and IL-1β synthesis, thus contributing to HDM/LPS-induced neutrophil-dominant airway inflammation.

show abstract

Clinical Trials and Regulatory Issues of Natural Polymers Employed in Respiratory Disease

Hussian

Tripathy

Dua

et al. 2023

Natural Polymeric Materials Based Drug Delivery Systems in Lung Diseases

View full text Add to dashboard Cite

Leukotriene B4 receptors play critical roles in house dust mites-induced neutrophilic airway inflammation and IL-17 production

Cited by 7 publications

References 33 publications

Leukotriene B4 Receptor 2 Mediates the Production of G-CSF That Plays a Critical Role in Steroid-Resistant Neutrophilic Airway Inflammation

Leukotriene B4 Receptor 2 Mediates the Production of G-CSF That Plays a Critical Role in Steroid-Resistant Neutrophilic Airway Inflammation

Leukotriene B4 Receptors Are Necessary for the Stimulation of NLRP3 Inflammasome and IL-1β Synthesis in Neutrophil-Dominant Asthmatic Airway Inflammation

Clinical Trials and Regulatory Issues of Natural Polymers Employed in Respiratory Disease

Contact Info

Product

Resources

About