title: Effects of topically applied rapamycin and mycophenolic acid on TNCB-induced atopic dermatitis-like skin lesions in NC/Nga mice.
abstract: Rapamycin (RPM) and mycophenolic acid (MPA) are immunosuppressive drugs approved for use in preventing transplant rejection. These drugs have also been used in the field of dermatology as glucocorticoid sparing agents for autoimmune and inflammatory disorders such as atopic dermatitis (AD). The aim of this study was to investigate the therapeutic effect of topically applied RPM and/or MPA on AD-like skin lesions in NC/Nga mice. RPM (0.04% - 4%), MPA (0.2% - 5%), and formulations of both agents at various ratios were administrated topically to NC/Nga mice with 2-chloro-1,3,5-trinitrobenzene (TNCB)-induced AD-like skin lesions. The therapeutic effects of topical RPM, MPA, and the mixed formulations in TNCB-treated NC/Nga mice were assessed by measuring skin severity scores, ear thickness, and histological changes in the lesioned skin including mast cell count and total serum IgE levels. Expression of interleukin (IL)-4, and interferon (IFN)-γ was also assessed. Topical 4% RPM and/or 1% MPA treatment significantly improved clinical signs of AD such as erythema, edema, excoriation, and dryness on day 29 (P<0.05). In addition, 4% RPM, 1% MPA, and the mixed formulations significantly decreased epidermal thickening, dermal edema, and cellular infiltration into the dermis compared with the vehicle. RPM (4%) and/or MPA (1%) significantly reduced the expression of IL-4 and IFN-γ mRNA and protein levels compared with the vehicle (P<0.05). No significant change in the levels of total serum IgE was induced by topical 4% RPM and/or 1% MPA. The present results demonstrated that topical 4% RPM and/or 1% MPA improved TNCB-induced AD-like lesions of NC/Nga mice by suppressing expression of Th2-related cytokines (IL-4) and Th1-related cytokines (IFN-γ). These findings suggest that RPM and/or MPA may be promising topical therapeutic candidates for the treatment of AD.
authors: Department of Dermatology, Eulji University Hospital, College of Medicine, Eulji University, 95 Dunsanseo-ro, 302-799 Daejeon, Republic of Korea.
authors: Kyung Eun
authors: KE
authors: Jung
authors: Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 505 Banpo-daero, 137-701 Seoul, Republic of Korea.
authors: Ye Jin
authors: YJ
authors: Lee
authors: Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 505 Banpo-daero, 137-701 Seoul, Republic of Korea.
authors: Yun Hee
authors: YH
authors: Ryu
authors: Department of Dermatology, St. Paul's Hospital, Seoul, College of Medicine,The Catholic University of Korea, 620-56 Jeonnong-dong, 130-709, Seoul, Korea.
authors: Jung Eun
authors: JE
authors: Kim
authors: Department of Dermatology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Dongsuro, Bupyeong-gu, 150-713 Incheon, Republic of Korea.
authors: Hei Sung
authors: HS
authors: Kim
authors: Department of Dermatology, Chung-Ang University Hospital, College of Medicine, Chung-Ang University, 102 Heukseok-ro, 156-755 Seoul, Republic of Korea.
authors: Beom Joon
authors: BJ
authors: Kim
authors: Department of Dermatology, St. Paul's Hospital, Seoul, College of Medicine,The Catholic University of Korea, 620-56 Jeonnong-dong, 130-709, Seoul, Korea.
authors: Hoon
authors: H
authors: Kang
authors: Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 505 Banpo-daero, 137-701 Seoul, Republic of Korea. Electronic address: yymmpark6301@hotmail.com.
authors: Young Min
authors: YM
authors: Park
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000188:drug therapy*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D007073:Immunoglobulin E / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D014301:Trinitrobenzenes / Q000008:administration & dosage
chemical_list: D007166:Immunosuppressive Agents; D007375:Interleukin-1; D014301:Trinitrobenzenes; D007073:Immunoglobulin E; D007371:Interferon-gamma; D009173:Mycophenolic Acid; D020123:Sirolimus
keywords: Atopic dermatitis; Mycophenolic acid; Rapamycin; Topical administration