Proinflammatory cytokine production in HaCaT cells treated by eosin: implications for the topical treatment of psoriasis.
Psoriasis is a multifactorial skin dermatosis characterized in its classical form by erythematous and hyperkeratotic plaques on extensor surfaces of the body, that in most cases can be managed therapeutically by topical agents. Hyperproliferation and a marked inflammation in both epidermis and dermis are thought to be driven by interaction of activated type-1 T lymphocytes and antigen-presenting cells and keratinocytes that release several proinflammatory and immunomodulating molecules. The aim of this study is to investigate whether tetrabromofluorecin, commonly know as eosin, a classical compound traditionally topically used in psoriasis for its presumed anti-inflammatory activities, is able to modulate the production of TNF-alpha, IL-6 and IL-8 that are recognized as the most active and characterized cytokines in the pathogenesis of this skin disorder. HaCaT cell line was used to verify the effects on epidermal inflammation by eosin at scalar doses after testing the viability of cells. Two different population of cells, one stimulated by IFNgamma and one non-stimulated, were cultivated in presence of tolerable concentrations. The expression and release of IL-6, IL-8, IL-10, and TNF-alpha were analysed by RT-PCR and ELISA, respectively. Our results show that tolerable concentrations of eosin were 0.05%, 0.02%, and 0.01%. The expression and production of TNFalpha, IL-8 and IL-6 were dramatically reduced in presence of eosin 0.05% and 0.02% and the action of eosin was more pronounced on TNF-alpha. In agreement with clinical data, our results show that in presence of tolerable concentrations, eosin seems to influence remarkably the production of three important cytokines involved in the hyperproliferation and inflammatory process, giving a specific explanation of its efficacy and supporting its topical use in the clinical setting.
Zampetti
A
A
Department of Dermatology, Catholic University of the Sacred Heart, Rome, Italy. anna.zampetti@gmail.com
Mastrofrancesco
A
A
Flori
E
E
Maresca
V
V
Picardo
M
M
Amerio
P
P
Feliciani
C
C
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D004801:Eosine Yellowish-(YS) / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D003879:Dermatologic Agents; D018836:Inflammation Mediators; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D004801:Eosine Yellowish-(YS)