Role of Toll-Like Receptor 4 (TLR4) in the Development of Inflammatory Process in Skin of Psoriasis Patients

R. L. Stepanenko

Abstract


The objective of the research was to study the mechanisms of developing local immune inflammation considering changes in immunohistochemical expression of Toll-like receptor 4 (TLR4) in skin of psoriasis patients after systemic immunosuppressive therapy.

Materials and methods. Immonohistochemical dynamic analysis of biopsy material taken from psoriaform skin areas in 62 psoriasis patients receiving systemic immunosuppressive therapy was made. Beyond that, to compare the results of the appropriate immunohistochemical examinations biopsy material from anterior abdominal wall taken after surgical intervention (e.g. hernia repair) in practically healthy persons of an appropriate age (5 patients) was studied. To determine the nature and area of local cellular immune and inflammatory reactions in skin of psoriasis patients, immunohistochemical techniques for determining TLR4 marker expression were used.

Results and discussion. While studying TLR4 expression, background diffuse cytoplasmic and nuclear staining of epidermis, vascular endothelium and single macrophage cells were identified in psoriaform skin areas. The number of positive-stained epidermis cells was about 80%. After a course of systemic suppressive therapy with Etanercept during 3 months, immunohistochemical reaction to identify TLR4 expression allowed us to establish that both the number of positive-stained cells and response intensity in epidermis considerably reduced. The number of cells expressing TLR4 in the epidermis was up to 60%. Even after treatment, a considerable number of TLR4-positive dendrite cells with a greatly increased size and extended with their processes up to the horny layer were identified in the epidermis.

Conclusions. The ligands activating toll-like receptors of macrophages and subsequent inflammatory reaction probably concentrate in epidermis dendrite cells as evidenced by immunohistochemical reactions. TLR4-positive macrophages after activation in dermal papilla migrate to the papilla base to be then included as a component of inflammatory perivascular infiltrates. After treatment, the number of cells (both dendrite and macrophage) with TLR expression significantly decreased. However, the background readiness to a burst of activity of toll-like receptors persists. 


Keywords


psoriasis; Toll-like receptors; systemic immunosuppressive therapy; immunohistochemical changes in skin

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