Corticosteroid enhances TNF-α-mediated leukocyte adhesion to pulmonary microvascular endothelial cells

A. Matsuda*, Kanami Orihara, S. Fukuda, H. Fujinaga, K. Matsumoto, H. Saito


研究成果: Article査読

27 被引用数 (Scopus)


Background: Some severe asthma patients are characterized by elevated levels of tumor necrosis factor alpha (TNF-α) and neutrophilic inflammation in the airways. Although such phenotypic changes in asthma might contribute to corticosteroid refractoriness, the role of TNF-α in the process remains unclear. TNF-α exerts its biological effects mainly by acting on the vascular endothelium, and thereby upregulates leukocyte recruitment into inflamed tissues. The aim of this study was to investigate the effects of dexamethasone (DEX) on the TNF-α-mediated responses of human microvascular endothelial cells from lung blood vessels (HMVEC-LBl) in vitro. Methods: HMVEC-LBl were cultured with TNF-α in the presence and absence of DEX. The effects of DEX on various TNF-α-mediated responses, such as the expressions of chemokines and cellular adhesion molecules, leukocyte adhesion were determined. Results: TNF-α significantly induced growth-related oncogene alpha (GRO-α), interleukin 8 (IL-8), regulated on activation, normal T-cell expressed and secreted (RANTES) and interferon-inducible protein 10 (IP-10) productions and cell surface expressions of intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) on HMVEC-LBl. TNF-α-induced GRO-α and IL-8 were slightly attenuated by DEX treatment (reaches to 89% and 79%, respectively), whereas expressions of IP-10, ICAM-1 and VCAM-1 were significantly enhanced by the same treatment (up to 172%, 152% and 139%, respectively). Correspondingly, in vitro adhesion of eosinophils and neutrophils to TNF-α-treated HMVEC-LBl were significantly enhanced by DEX. Conclusions: Some proinflammatory effects of DEX, a corticosteroid, were found in TNF-α-mediated in vitro reactions of pulmonary microvascular endothelial cells, i.e. chemokine productions and leukocyte adhesion. These in vitro results may explain, at least in part, the corticosteroid refractoriness accompanied by a marked increase in TNF-α production that is seen in severe asthmatic patients.

ジャーナルAllergy: European Journal of Allergy and Clinical Immunology
出版ステータスPublished - 2008 12月

ASJC Scopus subject areas

  • 免疫学
  • 免疫アレルギー学


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