[Influence of peroxisome proliferator-activated receptor gamma on airway inflammation of guinea pigs with asthma].
OBJECTIVE
To investigate the influence and mechanism of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and its ligand agonist rosiglitazone on airway inflammation of guinea pigs with asthma.


METHODS
35 guinea pigs were divided into 5 groups by random number meter: a control group (A group), an asthma group (B group), a dexamethasone (DXM) group (C group), a rosiglitazone group (D group), and a rosiglitazone + 1/2 DXM group (E group), with 7 guinea pigs in each. Bronchoalveolar lavage (BAL) cell count and differential was studied, and the pathologic alteration of the bronchi and the lung tissue was observed. The expression of PPAR-gamma, COX-2 was measured by RT-PCR.


RESULTS
BAL eosinophil count was 0.050 +/- 0.020 in D group, 0.110 +/- 0.020 in B group, the difference being significantly (t = 5.61, P < 0.001). The total cell number and neutrophils were (15.5 +/- 3.9) x 10(8)/L and 0.069 +/- 0.020 in D group, and (19.9 +/- 4.3) x 10(8)/L and 0.076 +/- 0.020 in B group, the difference being not significant (t = 2.02, 0.66, P > 0.05 respectively). The thickness of airway wall of D group was (22.0 +/- 5.0) micro m, and in B group it was (28.0 +/- 5.0) micro m, the difference being significant (t = 2.61, P < 0.05), but the thickness of mucosa and submucosa of D group (12.2 +/- 2.9) micro m was not different as compared with B group (14.9 +/- 3.3) micro m (t = 1.63, P > 0.05). Expression of PPAR-gamma mRNA of D group 19.5 +/- 3.0 was not different compared with B group 18.1 +/- 3.1 and A group 15.6 +/- 2.9 respectively (t = 0.92, 0.49, P > 0.05, respectively). When the expression of COX-2 mRNA of B group 49 +/- 7 was compared with D group 39 +/- 6, the difference was significant (t = 2.77, P < 0.05).


CONCLUSIONS
Rosiglitazone decreases airway eosinophils and the thickness of airway wall in guinea pigs with asthma, via suppression of COX-2 mRNA expression by activating PPAR-gamma. The anti-inflammatory effect of PPAR-gamma may be associated with the use of ligand agonist and(or) glucocorticoids.
Bao
Zhi-jian
ZJ
Department of Respiratory Medicine, Xiangya Second Hospital, Central South University, Changsha 410011, China.
Xiang
Xu-dong
XD
Deng
Jun-wei
JW
Yan
Shu-zhen
SZ
Chen
Ping
P
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D051546:Cyclooxygenase 2; D004804:Eosinophils / Q000166:cytology; D005260:Female; D006168:Guinea Pigs; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D007527:Isoenzymes; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases