[The expression and regulation of vascular cell adhesion molecules and eotaxin in bronchioles and lung tissue from a guinea-pig model of asthma].
OBJECTIVE
To evaluate the expression of vascular cell adhesion molecules (VCAM-1) and eotaxin and their transcription factors NF-kappa B and AP-1 in bronchi and bronchioles (with surrounded lung tissue), and to investigate the mechanisms for eosinophil chemotaxis to the lungs in a guinea pig model of asthma.


METHODS
(1) The guinea pig model of asthma was established by the ovalbumin challenge method. (2) The animal models were divided into six groups: control, asthma day 1, asthma day 4, asthma day 14, intraperitoneal dexamethasone, and budesonide inhalation groups. (3) The protein expressions of VCAM-1, eotaxin, NF-kappa B and AP-1 in segmental bronchi and in bronchioles and lung tissue were measured by immunohistochemical techniques. (4) The mRNA expressions of VCAM-1 and eotaxin in lung tissue homogenates were determined by RT-PCR. (5) The DNA binding activities of NF-kappa B and AP-1 were measured by electrophoretic mobility shift assay (EMSA).


RESULTS
(1) In all the asthmatic groups, the protein levels of VCAM-1, eotaxin, NF-kappa B and AP-1, expressed both in central and peripheral airways (26.3 +/- 3.2, 89.0 +/- 8.6, 179 +/- 7 and 76 +/- 6), were significantly elevated compared to those in the control group (11.2 +/- 3.7, 5.0 +/- 4.0, 36 +/- 3 and 27 +/- 5). (2) The mRNA expression levels of VCAM-1 and eotaxin in lung tissue homogenates were significantly higher in the asthmatic groups (2.46 +/- 0.38 and 1.080 +/- 0.080) than those in the control group (1.05 +/- 0.11 and 0.080 +/- 0.020). (3) The DNA binding activities of NF-kappa B and AP-1 were significantly increased in the asthmatic groups (256 +/- 10 and 78 +/- 14), than those in the control group (67 +/- 13 and 12 +/- 3). (4) All these parameters in both glucocorticoid treated groups were significantly decreased compared to those in the asthma day 14 group, and similar to those in the control group.


CONCLUSIONS
VCAM-1 and eotaxin actively participated in the process of eosinophilic inflammation. NF-kappa B and AP-1 may play important roles in the regulation of VCAM-1 and eotaxin. The up- regulation of these inflammatory mediators existed not only in central airways, but also in small airways and lung tissue, indicating that asthma in this model is a disease of whole respiratory system. Glucocorticoids, either by systemic use or inhalation, demonstrated antiinflammatory effects by inhibiting the expressions and activities of NF-kappa B and AP-1 and by down-regulation of VCAM-1 and eotaxin.
Cui
Dejian
D
Division of Respirology, 304 Hospital, Beijing 100037, China.
Zeng
Zerong
Z
D000818:Animals; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000032:analysis* / Q000235:genetics; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018808:Transcription Factor AP-1 / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis* / Q000235:genetics
D054413:Chemokine CCL11; D019742:Chemokines, CC; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D019010:Vascular Cell Adhesion Molecule-1; D004247:DNA