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Leukotriene B4 receptors contribute to house dust mite-induced eosinophilic airway inflammation via TH2 cytokine production

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초록

Leukotriene B4 (LTB4) is a lipid mediator of inflammation thatis generated from arachidonic acid via the 5-lipoxygenase pathway. Previous studies have reported that the receptors of LTB4,BLT1, and BLT2 play mediatory roles in the allergic airwayinflammation induced by ovalbumin (OVA). However, consideringthat house dust mites (HDMs) are the most prevalent allergenand well-known risk factor for asthmatic allergies, we are interestedin elucidating the contributory roles of BLT1/2 in HDMinducedallergic airway inflammation. Our aim in this studywas to investigate whether BLT1/2 play any roles in HDM-inducedallergic airway inflammation. In this study, we observed thatthe levels of ligands for BLT1/2 [LTB4 and 12(S)-HETE (12(S)-hydroxyeicosatetraenoic acid)] were significantly increased inbronchoalveolar lavage fluid (BALF) after HDM challenge. Blockadeof BLT1 or BLT2 as well as of 5-lipoxygenase (5-LO) or12-lipoxygenase (12-LO) markedly suppressed the productionof TH2 cytokines (IL-4, IL-5, and IL-13) and alleviated lunginflammation and mucus secretion in an HDM-induced eosinophilicairway-inflammation mouse model. Together, these resultsindicate that the 5-/12-LO-BLT1/2 cascade plays a role in HDMinducedairway inflammation by mediating the production ofTH2 cytokines. Our findings suggest that BLT1/2 may be apotential therapeutic target for patients with HDM-inducedallergic asthma.

Abstract

Leukotriene B4 (LTB4) is a lipid mediator of inflammation thatis generated from arachidonic acid via the 5-lipoxygenase pathway. Previous studies have reported that the receptors of LTB4,BLT1, and BLT2 play mediatory roles in the allergic airwayinflammation induced by ovalbumin (OVA). However, consideringthat house dust mites (HDMs) are the most prevalent allergenand well-known risk factor for asthmatic allergies, we are interestedin elucidating the contributory roles of BLT1/2 in HDMinducedallergic airway inflammation. Our aim in this studywas to investigate whether BLT1/2 play any roles in HDM-inducedallergic airway inflammation. In this study, we observed thatthe levels of ligands for BLT1/2 [LTB4 and 12(S)-HETE (12(S)-hydroxyeicosatetraenoic acid)] were significantly increased inbronchoalveolar lavage fluid (BALF) after HDM challenge. Blockadeof BLT1 or BLT2 as well as of 5-lipoxygenase (5-LO) or12-lipoxygenase (12-LO) markedly suppressed the productionof TH2 cytokines (IL-4, IL-5, and IL-13) and alleviated lunginflammation and mucus secretion in an HDM-induced eosinophilicairway-inflammation mouse model. Together, these resultsindicate that the 5-/12-LO-BLT1/2 cascade plays a role in HDMinducedairway inflammation by mediating the production ofTH2 cytokines. Our findings suggest that BLT1/2 may be apotential therapeutic target for patients with HDM-inducedallergic asthma.

참고문헌 (39)

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