DNA vaccine encoding Der p2 allergen down-regulates STAT6 expression in mouse model of allergen-induced allergic airway inflammation.
BACKGROUND
Activation of signal transducer and activator of transcription 6 (STAT6) plays a critical role in the late phase of Th2-dependent allergy induction. STAT6 is essential to Th2 cell differentiation, recruitment, and effector function. Our previous study confirmed that DNA vaccination inhibited STAT6 expression of spleen cells induced by allergen. In the present study, we determined whether DNA vaccine encoding Dermatophagoides pteronyssinus group 2 (Der p2) could down-regulate the expression and activation of STAT6 in lung tissue from asthmatic mice.


METHODS
After DNA vaccine immunization, BALB/c mice were sensitized by intraperitoneal injection and challenged by intranasal instillation of rDer p2. The levels of the cytokines IL-4 and IL-13 in BAL fluid were measured by enzyme-linked immunosorbent assay. The lung tissue was assessed by immunohistochemical staining with anti-STAT6. The protein expression of STAT6 was determined by Western blot. The activation of STAT6 binding ability was analyzed with electrophoretic mobility shift assay.


RESULTS
DNA vaccine encoding Der p2 allergen effectively decreased the levels of IL-4 and IL-13 in the asthmatic mice. Histological evidence and Western blot showed that the expression of STAT6 in the DNA treated mice was markedly attenuated. STAT6 binding to specific DNA motif in lung tissue from the gene vaccinated mice was inhibited.


CONCLUSIONS
DNA vaccine encoding Der p2 prevents allergic pulmonary inflammation probably by inhibiting the STAT6 signaling pathway in mice with Der p2 allergen-induced allergic airway inflammation.
College of Life Sciences, Shenzhen University, Shenzhen 518060, China.
Jing
J
Qiu
Guo-ping
GP
Li
Zhi-gang
ZG
Liu
Pei-xing
PX
Ran
Nan-shan
NS
Zhong
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000235:genetics* / Q000276:immunology; D060829:Arthropod Proteins; D001249:Asthma / Q000517:prevention & control*; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D018793:Interleukin-13 / Q000037:antagonists & inhibitors; D015847:Interleukin-4 / Q000037:antagonists & inhibitors; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D050800:STAT6 Transcription Factor / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D015398:Signal Transduction; D014611:Vaccination; D019444:Vaccines, DNA / Q000627:therapeutic use*
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C451163:Dermatophagoides pteronyssinus antigen p 2; D018793:Interleukin-13; D050800:STAT6 Transcription Factor; D019444:Vaccines, DNA; D015847:Interleukin-4