کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3214304 1203282 2007 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeting TNFα rapidly reduces density of dendritic cells and macrophages in psoriatic plaques with restoration of epidermal keratinocyte differentiation
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
پیش نمایش صفحه اول مقاله
Targeting TNFα rapidly reduces density of dendritic cells and macrophages in psoriatic plaques with restoration of epidermal keratinocyte differentiation
چکیده انگلیسی

SummaryBackgroundThe cytokine network theory for psoriasis postulates a key role for TNFα in mediating inflammation and altered epidermal differentiation.ObjectiveThis study defines responses following administration of adalimumab, a TNFα inhibitor, in pre-psoriatic skin (PN) and lesional psoriatic plaques (PP) skin.MethodsPN and PP skin before and after treatment were biopsied at days 2, 7, 28 and 84 (n = 6 different patients). Cryosections were immunohistochemically stained to detect TNFα and other relevant markers in epidermal and dermal compartments. Detection of apoptosis utilized antibody specific for activated caspase 3. Semiquantitative assessments and statistical analysis was performed for each staining profile.ResultsTNFα+ cells were increased in PP skin. PP skin was also characterized by a four-fold increase in number of CD68+ macrophages as well as eight-fold increase in CD11c+ dermal dendritic cells (DCs) compared to PN skin. By two-color immunofluorescence staining, both CD68+ cells as well as CD11c+ cells expressed TNFα. Following initiation of adalimumab therapy, CD11c+ cells, significantly decreased in PP skin at days 7, 28, and 84, while CD68+ and CD14+ cells decreased at days 28 and 84. Other markers for DCs (CD83, CD86) showed decreases at days 7, 28, and 84. Reduction in DCs, macrophages or T cells was not accompanied by increased activated caspase 3-positive cells. When a keratinocyte terminal differentiation marker was examined, adalimumab triggered rapid restoration of loricrin expression (beginning on day 2), with loss of aberrant differentiation marker, keratin 17 (K17).ConclusionAdalimumab impacts dermal-based immunocytes, and the epidermal compartment also responds by restoration of normal differentiation without detectable apoptosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Dermatological Science - Volume 48, Issue 2, November 2007, Pages 87–101
نویسندگان
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