Activation of PPARγ by restores mast cell numbers and reactivity in alloxan-diabetic rats by reducing the systemic glucocorticoid levels.
Mast cell function and survival have been shown to be down-regulated under diabetic conditions. This study investigates the role of the peroxisome proliferator-activated receptor (PPAR)-γ in reducing mast cell number and reactivity in diabetic rats. The effect of rosiglitazone on mast cell apoptosis was also evaluated. Diabetes was induced by intravenous injection of alloxan into fasted rats and PPARγ agonist rosiglitazone and/or specific antagonist 2-chloro-5-nitrobenzanilide (GW9662) were administered 3 day after diabetes induction, once daily for 18 consecutive days. Mast cell apoptosis and plasma corticosterone levels were evaluated by TUNEL and radioimmunoassay, respectively. Treatment with rosiglitazone restored mast cell numbers in the pleural cavity and mesenteric tissue of diabetic rats. Rosiglitazone also significantly reversed the diabetes-induced reduction of histamine release by mast cells, as measured by fluorescence, following activation with the antigen in vitro. Increased apoptosis in mast cells from diabetic rats were inhibited by rosiglitazone. Moreover, we noted that the increase in plasma corticosterone levels in diabetic rats was inhibited by rosiglitazone. In addition, GW9662 blocked the ability of rosiglitazone to restore baseline numbers of mast cells and plasma corticosterone in diabetic rats. In conclusion, our findings showed that rosiglitazone restored the number and reactivity of mast cells in diabetic rats, accompanied with a suppression of apoptosis, in parallel with impairment of diabetes hypercorticolism, indicating that PPARγ has an important role in these phenomena.
Laboratório de Inflamação, Brazil.
Rafael C
RC
Torres
Marcelo M
MM
Batista
Andrea H
AH
Pons
Adriana R
AR
Silva
Renato S B
RS
Cordeiro
Marco A
MA
Martins
Patrícia M R
PM
E Silva
Vinicius F
VF
Carvalho
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003480:Cushing Syndrome / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects*; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use
D005938:Glucocorticoids; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone