TNFAIP3/A20 expression in allergic asthma

Introduction: A20/tumour necrosis factor alpha-induced protein 3 (TNFAIP3) is an intracellular ubiquitin-editing protein that reduces activation of NF-B. A20 is reported to be protective in allergy and asthma. We measured the expression of A20 in allergic mice, in human lung biopsies and in blood leukocytes collected from asthmatic patients. Methods: BALB/c mice were sensitized twice with ovalbumin (OVA) and challenged on days 14-16 and then again 10, 20 or 30 days later. Bronchoalveolar lavage was performed 24h after last challenge in each group. Using immunohistochemistry methods, mouse and human lung tissue were stained with anti-A20 antibody and revealed by DAB. Expression of A20 in peripheral blood from healthy and asthmatic donors was measured by flow cytometry. Results: there is a significant increase in the number of eosinophils in the lung of OVA mice at day 1, 10 and 20 but not at day 30 (sham: ND, OVA 24h: 98+7*, 10 days: 102+4*, 20 days: 44+7*, 30 days: 37+12 cells x 104/ml, n=4/group, p<0.001). The expression of A20 in the lung tissue inversely correlated with eosinophil migration (OVA 24h: 10.3+2.3, 10 days: 11+1, 20 days: 29+3*, 30 days: 33+1*, % area, n=4/group, p<0.01). A20 expression in asthmatic human lung is significantly lower in comparison to healthy subjects (healthy: 44+5, asthmatics: 22+2 % area, n=3/group, p<0.0001). A20 expression measured by flow cytometry demonstrated a lower level of A20 in asthma leukocytes in comparison to healthy (healthy: 21+6, asthmatics: 7+2, % expression, n=10-9/group, p<0.05). Conclusion: Our results showed a lower expression of A20 in allergic mice and asthmatic patients, supporting the hypothesis that this protein has a protective effect on asthma and allergy.