Administration of mycobacterial Ag85A and IL-17A fusion protein  attenuates airway inflammation in a murine model of asthma.
Interleukin (IL)-17A contributes to the development of asthma, especially in severe asthma which has characteristic neutrophil infiltration in airways. However, IL-17A-blocking antibody could escalate T helper (Th) 2 cytokines, such as IL-13, IL-4 in murine models. We aimed at determining the effect of mycobacterial Ag85A and IL-17A fusion protein—Ag85A-IL-17A on airway inflammation in a murine model of asthma. IL-17A recombinant protein fused mycobacterial immunodominant antigen Ag85A was constructed, expressed and purified. The fusion protein was then administrated into BALB/c mice and its anti-inflammatory effects in the infiltration of inflammatory cells, Th2/Th17 cytokines in BALF, histopathological changes of lung tissues as well as chemokines in lung tissues were evaluated in the murine model of asthma. We found that administration of mycobacterial Ag85A and IL-17A fusion protein induced IL-17A specific immunoglobulin (Ig)G in sera and significantly decreased IL-17A and IL-6 levels in bronchoalveolar lavage fluid (BALF). Ag85A-IL-17A vaccinated mice also showed marked reduction in the infiltration of inflammatory cells in peribronchiolar region and significant decrease in total cells, eosinophil cells and neutrophil cells in BALF. The increased levels of IL-13 and IL-4 in BALF of ovalbumin-sensitized mice were significantly reduced by the administration of Ag85A-IL-17A. Furthermore, CD3+CD4+IL-13+ splenocytes stimulated with OVA and CXCL1 mRNA, CCL2 mRNA and GATA-3 mRNA expressed in lung tissues were decreased markedly in Ag85A-IL-17A vaccinated group. Our results demonstrate remarkable antiallergic effects of Ag85A-IL-17A in a murine model of asthma and it may have protective effects on allergic asthma.
Rong
R
Jin
Sheng
S
Guo
Mei-yi
MY
Wang
Yan-hua
YH
Li
Liang-Xia
LX
Wu
Hui
H
Ma
Douglas B
DB
Lowrie
Xiao-yong
XY
Fan
Jian-hua
JH
Zhang
D000217:Acyltransferases / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D000485:Allergens; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics; D054360:Chemokine CXCL1 / Q000235:genetics; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D012333:RNA, Messenger / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000485:Allergens; D000893:Anti-Inflammatory Agents; D000942:Antigens, Bacterial; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007074:Immunoglobulin G; D020381:Interleukin-17; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D010047:Ovalbumin; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis