Topical Tetracycline Improves MC903-induced Atopic Dermatitis in Mice through Inhibition of Inflammatory Cytokines and Thymic Stromal Lymphopoietin Expression.
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. Western 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.
Department of Dermatology, Peking University People's Hospital, Beijing 100044, China.
Xiao-Jing
XJ
Liu
Department of Dermatology, Peking University People's Hospital, Beijing 100044, China.
Zhang-Lei
ZL
Mu
Department of Dermatology, Peking University People's Hospital, Beijing 100044, China.
Yan
Y
Zhao
Department of Dermatology, Peking University People's Hospital, Beijing 100044, China.
Jian-Zhong
JZ
Zhang
D000287:Administration, Topical; D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives / Q000633:toxicity; D016207:Cytokines; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013754:Tetracyclines / Q000008:administration & dosage / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D018793:Interleukin-13; D013754:Tetracyclines; D014409:Tumor Necrosis Factor-alpha; C055085:calcipotriene; D015847:Interleukin-4; D002117:Calcitriol; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse