Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation

Abstract

Endothelin‐1 (ET‐1) is a strong bronchoconstrictor which possesses pro‐inflammatory properties and is claimed to be an important mediator in bronchial asthma. The present study was undertaken to investigate whether ET‐1 synthesis, in an inflammation dominated by neutrophilic granulocytes, is as pronounced as previously demonstrated in an airway inflammation dominated by eosinophils. Moreover, the authors compared the production of ET‐1 and tumour necrosis factor (TNF)‐α in rat lungs following intratracheal instillation of either lipopolysaccharide (LPS) (neutrophilic inflammation) or Sephadex (SDX) (eosinophilic). The lung tissue ET‐1 messenger ribonucleic acid (mRNA) expression was not increased in LPS treated animals whereas a six‐fold increase was measured after 30 min in the SDX group (p<0.05). TNF‐α mRNA signals increased early following LPS instillation, peaking at 2 h, whereas elevated TNF‐α mRNA in the SDX model was observed at 24 h. The ET‐1 concentrations in bronchoalveolar lavage fluid (BALF) rose slightly, but significantly, 3 h after both LPS and SDX exposure. At 24 h no further rise in ET‐1 levels was observed in the LPS model, while a substantial increase in the ET‐1 concentration was measured in the SDX group (p<0.05). The TNF‐α concentrations in BALF rose considerably at 3 h in the LPS group, but was nearly abolished at 24 h. In SDX challenged animals however, an increase in BALF‐TNF‐α did not occur until 24 h postchallenge. In conclusion, intratracheal instillation of lipopolysaccharide, leading to a purely neutrophilic lung inflammation, does not induce synthesis of endothelin‐1. This is in contrast to observations during an eosinophilic airway inflammation, indicating a specific role of endothelin‐1 in lung inflammations dominated by eosinophils. In contrast to in vitro experiments, no evidence for induction of endothelin‐1 synthesis was observed by high levels of tumour necrosis factor‐αin vivo.

Critical Role for T Cells in Sephadex-Induced Airway Inflammation: Pharmacological and Immunological Characterization and Molecular Biomarker Identification

“…The increase in eosinophil influx to lung tissue was apparent 6 h after challenge and remained elevated at least 72 h after treatment in confirming previous reports (16,18,26,27). Our data also demonstrate an accumulation of T cells, including CD4 ϩ (helper) T cells, in lung tissue.…”

Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway

“…Therefore, more detailed studies are needed to better characterize whether IL-10 has antihypertensive properties in this experimental model. TNF-␣ was chronically infused to induce increased ET-1 expression, as previously described (2,10,18,29,47,51). We used prepro-ET-1 mRNA as a biomarker for ET-1 levels, since increased ET-1 plasma values may not reflect local production (12,30).…”

Effect of bosentan on the production of proinflammatory cytokines in a rat model of emphysema

“…After embedding in paraffin, the tissues were cut into 5 µm sections and stained with hematoxylin-eosin methods and assessed under a light microscope (Finsnes et al, 2000).…”