Effects of antiallergic herbal agents on cystic fibrosis transmembrane conductance regulator in nasal mucosal epithelia of allergic rhinitis rabbits.
BACKGROUND
It has been found that the expression of cystic fibrosis transmembrane conductance regulator (CFTR) is closely related to allergic rhinitis (AR). In the previous study, we have demonstrated that antiallergic herbal agents (AHA) can obviously inhibit the allergic reaction of AR. The aim of this study was to explore the expression of CFTR and the effects of AHA on CFTR to improve the allergic reaction of AR.


METHODS
An animal model of an AR rabbit was established using ovalbumin (OVA). The rhinitis rabbits were randomly assigned to three groups: AHA treating group (AHATG), modeling group (MG) and healthy controlling group (HCG). The expressions of CFTR protein were examined by immunohistochemical method. The mucosal epithelial cells of all the rabbits were primarily cultured with tissue culture method in vitro and treated with or without glibenclamide for 24 hours. The levels of monocyte chemotactic factor-1 (MCP-1) and RANTES protein in supernatants of culture were measured by ELISA, and the expressions of CFTR mRNA were detected by real-time PCR.


RESULTS
The expressions of CFTR mRNA and protein greatly increased in mucosal epithelial cells of MG. The protein concentrations of MCP-1, RANTES in culture supernatants of MG were significantly higher than those in the other two groups (P < 0.01), and they reached much higher level than those at the start points in the MG (P < 0.05) and were significantly different compared with those in the AHATG after being cultured for 24 hours (P < 0.01). CFTR mRNA in MG + glibenclamide were much lower than those in MG (P < 0.05). RANTES and CFTR mRNA treated with glibenclamide in AHATG were significantly lower than those in the AHATG (P < 0.01). Minimal changes in the secretions of MCP-1 in the epithelial cells were detected between AHATG and AHATG + glibenclamide (P > 0.05).


CONCLUSIONS
AHA can inhibit the secretions of CFTR, RANTES and MCP-1 in mucosal epithelia and improve inflammatory reaction of AR. CFTR may play an important role in the secretion of RANTES and mucosal inflammatory response in AR. Glibenclamide can inhibit the CFTR secretion in mucosal epithelial cells, in particular during AR process. These effects of glibenclamide on secretion of RANTES can be effectively strengthened by AHA.
Li
Qiang
Q
School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
Li
Xiao-Li
XL
Yang
Xue
X
Bao
Jian-Min
JM
Shen
Xiao-Hong
XH
D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005905:Glyburide / Q000494:pharmacology / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D011897:Random Allocation; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000378:metabolism*
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D004365:Drugs, Chinese Herbal; C495667:MCP1 protein, rabbit; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005905:Glyburide