Background:Tetracycline (TET) has been found to have both antibiotic and anti-inflammatory properties.The anti-inflammatory effect of topical TET on atopic dermatitis (AD) has not been reported.The purpose of this study was to explore the potential role of topical TET and its anti-inflammatory effects in a mouse model of AD.Methods:The 2％ TET was applied topically to ears of MC903-induced AD-like BALB/c mice once a day.AD-like symptoms and severity were evaluated by assessing skin scoring of dermatitis,ear thickness,and frequency of scratching.Serum IgE and thymic stromal lymphopoietin (TSLP) levels were measured by enzyme-linked immunosorbent assay.West blot was used for analyzing the expressions of TSLP,protease-activated receptor 2 (PAR2),and nuclear factor-kappa B (NF-κB) in skin lesions.Real-time polymerase chain reaction was performed to assess the mRNA levels of TSLP and inflammatory cytokines including interleukin (IL)-4,IL-13,tumor necrosis factor (TNF)-α,and IL-1β in skin lesions.Results:Scoring of dermatitis (9.00 ± 0.63 vs.6.67 ± 1.03,P =0.001),ear thickness (0.44 ± 0.02 mm vs.0.40 ± 0.03 mm,P =0.018),and serum IgE level (421.06 ± 212.13 pg/ml vs.244.15 ± 121.39 pg/ml,P =0.047) were all improved in the 2％ TET treatment group compared with AD group.Topical TET significantly reduced the serum level of TSLP (119.04 ± 38.92 pg/ml vs.65.95 ± 54.61 pg/ml,P =0.011) and both mRNA and protein expressions of TSLP in skin lesions compared with AD group (P =0.003 and 0.011,respectively),and NF-κB and PAR2 expression in skin lesions were also suppressed (P =0.016 and 0.040,respectively).Furthermore,expressions of inflammatory cytokines IL-4,IL-13,and TNF-α in skin lesions were down-regulated in 2％ TET group compared with AD group (P =0.035,0.008,and 0.044,respectively).Conclusions:Topical TET exerted anti-inflammatory effects through suppression of TSLP and inflammatory cytokines in AD mouse model,suggesting TET as a potential agent for the topical treatment of AD in the future.