Abstract
This study was conducted to monitor the macrophage infiltration of atopic dermatitis (AD)-like skin lesions and to evaluate the effects of anti-AD therapeutic agents in immunocompetent mice via optical reporter-gene-based molecular imaging. The enhanced firefly luciferase (effluc)-expressing macrophage cell line (Raw264.7/effluc) was intravenously introduced into mice with 2,4-dinitrochlorobenzene (DNCB)-induced AD, followed by bioluminescent imaging (BLI). After in vivo imaging, AD-like skin lesions were excised, and ex vivo imaging and Western blotting were conducted to determine the presence of infused macrophages. Finally, the therapeutic effect of dexamethasone (DEX), an AD-modulating agent, was evaluated via macrophage tracking. In vivo imaging with BLI revealed the migration of the reporter macrophages to DNCB-induced AD-like skin lesions on day 1 post-transfer. The greatest recruitment was observed on day 3, and a decline in BLI signal was observed on day 14. Notably, in vivo BLI clearly showed the inhibition of the reporter macrophage infiltration of DNCB-induced AD-like skin lesions by DEX, which was consistent with the reduced AD symptoms observed in DEX-treated mice. We successfully visualized the macrophage migration to DNCB-induced AD-like skin lesions, proving the feasibility of macrophage imaging for evaluating AD-regulating drugs in living organisms.
Highlights
Atopic dermatitis (AD) is a global health problem, and ~20% of patients with AD throughout the world are teenagers and children [1,2]
Among various optical reporter genes, the enhanced firefly luciferase gene has been extensively investigated for tracking immune cells in living mice with various diseases because it can be used to detect a small number of injected immune cells in vivo
Owing to the highly sensitive optical reporter genes, we observed the first reporter macrophage infiltration of AD-like lesions on day 3 post-transfer and monitored their localization in AD-like lesions on day 14, which was consistent with the results of ex vivo imaging of DNCB-treated lesions and immunoblotting analysis using anti-luciferase antibodies
Summary
Atopic dermatitis (AD) is a global health problem, and ~20% of patients with AD throughout the world are teenagers and children [1,2]. AD is mainly identified as a disease of children, an increasing number of reports indicate that it is more common in adults than was previously thought, the prevalence being 3.2% and 10.2% in the adult population in the United States. AD caused by increased serum immunoglobulin E (IgE), inflammatory cytokine, and histamine levels is generally a chronic inflammatory skin disease, characterized by the symptoms of erythematous, pruritic, and excoriated papules [3,4,5,6,7]. Therapeutic approaches for AD have been dependent on the application of local or systemic corticosteroids [8]. These therapeutic strategies have several side effects in AD patients. Many attempts have been made to develop anti-AD agents for overcoming the limitations of clinical drugs currently used against AD, clinical therapeutic outcomes have remained unsatisfactory [9]
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