CD40 and OX40 ligand are increased on stimulated asthmatic airway smooth muscle

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:115

Article

Burgess, JK ; Blake, AE ; Boustany, S ; Johnson, PRA ; Armour, CL ; Black, JL ; Hunt, NH ; Hughes, JM

关键词: asthma;    inflammation;    CD40;    OX40 ligand;    TNF;    IL-1 beta;    prostaglandin E-2;    human airway smooth muscle cells;   

DOI  :  10.1016/j.jaci.2004.11.004

来源: Elsevier

【 摘 要 】

Background: Severe, persistent asthma is characterized by airway smooth muscle hyperplasia, inflammatory cell infiltration into the smooth muscle, and increased expression of many cytokines, including IL-4, IL-13, IL-1beta, and TNF-alpha. These cytokines have the potential to alter the expression of surface receptors such as CD40 and OX40 ligand on the airway smooth muscle cell. Objective: To examine whether cytokines alter expression of CD40 and OX40 ligand on airway smooth muscle cells and identify any differences in response between asthmatic and nonasthmatic airway smooth muscle cells. Methods: We used How cytometry and immunohistochemistry to detect CD40 and OX40 ligand on airway smooth muscle cells cultured in the presence of TNF-alpha, IL-1beta, IL-4, or IL-13. Prostaglandin E-2 levels were assessed by ELISA. Results: TNF-alpha increased expression of both CD40 and OX40 ligand on both asthmatic and nonasthmatic airway smooth muscle cells. The level of expression was significantly greater on the asthmatic cells. IL-1beta alone had no effect, but it attenuated the TNF-induced expression of both CD40 and OX40 ligand. The mechanism of inhibition was COX-dependent for CD40 and was COX-independent but cyclic AMP-dependent for OX40 ligand. IL-4 and IL-13 had no effect. Conclusion: Our study has demonstrated that TNF-alpha and IL-1beta have the potential to modulate differentially the interactions between cells present in the inflamed airways of a patient with asthma and therefore to contribute to the regulation of airway inflammation and remodeling.

【 授权许可】

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