Receptors In Lesions Research Articles

Expression of Toll-like receptors in lesions of condyloma acuminatum

Objective To measure the expressions of Toll like receptors (TLRs) in lesions of condyloma acuminatum (CA). Methods Tissue samples were resected from lesions of 25 patients with CA and normal skin of 16 human controls. Frozen sections were prepared and the expressions of TLRs 1 - 10 were measured by immunohistochemical staining. Results In normal skin samples, there was a strong expression of TLR 6 and 9, medium expression of TLR 1, 3, 10 and weak expression of TLR 2, 4, 5, 7, 8 in the stratum corneum and stratum granulosum, but a weak or negative expression of TLRs in the stratum spinosum and stratum basale. In contrast, a strong expression of TLR 1, 3, 6, 9, medium expression of TLR 4, 8, 10 and weak expression of TLR 2, 5, 7 were detected in keratinocytes of almost all epidermal layers except for stratum basale in CA lesions. Conclusions The expressions of TLRs, especially TLR 1, 3, 6, 9, are markedly enhanced in proliferated keratinocytes in CA lesions compared with normal skin, which is likely to be associated with anti-viral immunity triggered by HPV infection. Key words: Toll-like receptors; Condylomata acuminata; Staining and labeling; Papillomaviridae

Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin

Th17 cells are a lineage of proinflammatory T helper cells producing interleukin (IL)-17. The importance of Th17 cells in inflammation and autoimmunity has now been recognized. The IL-17 cytokine family consists of six isoforms (IL-17A-IL-17F) whereas five members of the IL-17 receptor (IL-17R) family have been identified (IL-17RA-IL-17RE). To characterize the expression of the IL-17 isoforms and receptors in lesional and nonlesional psoriatic skin. Methods Keratome and punch biopsies taken from patients with psoriasis were examined by enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction in order to measure the IL-17 isoforms and receptors. We demonstrated significantly increased mRNA expression of IL-17A, IL-17C and IL-17F in psoriatic skin. In contrast, the mRNA expression of IL-17B and IL-17D was significantly decreased in lesional compared with nonlesional skin, while IL-17E mRNA was undetectable. The increased mRNA expression of IL-17A, IL-17C and IL-17F was paralleled by an increased protein accumulation of these cytokines in psoriatic skin. Analysis of the IL-17R mRNA expression revealed significantly impaired mRNA expression of IL-17RB, IL-17RC, IL-17RD and IL-17RE in lesional psoriatic skin, whereas the mRNA expression of IL-17RA was similar in lesional and nonlesional psoriatic skin. This study characterizes the mRNA profile of the IL-17 isoforms and receptors in psoriatic skin lesions. Furthermore, we demonstrate for the first time augmented protein levels of IL-17A, IL-17C and IL-17F in psoriatic skin lesions, indicating a possible role for IL-17C in addition to IL-17A and IL-17F in the pathogenesis of psoriasis.

Identification of a Commonly Used CDR3 Region of Infiltrating T Cells Expressing Vβ13 and Vβ15 Derived From Psoriasis Patients

Psoriasis is a common inflammatory skin disease that is thought to be mediated by activated T cells. In this study, the complementarity-determining region 3 (CDR3) in T cell receptors was examined for a common sequence motif among the T cells infiltrated in psoriatic lesional skin. A common specific CDR3 motif (Vbeta13-DWTSGV-Jbeta2.7) in lesions from psoriasis patients was identified by polymerase-chain-reaction-based spectratyping analysis and DNA sequencing. In addition, VDJ rearrangement with highly homologous amino acid composition in the CDR3 was observed in Vbeta15 of T cell receptors in lesions derived from psoriatic patients. Remarkably, T cell receptors containing the Vbeta13-DWTSGV-Jbeta2.7 were also found in the clinically normal skin from the psoriasis patients, which might seem to be responsible for the artificial production of psoriatic lesions. The identified CDR3 motif was highly expressed in cutaneous lymphocyte antigen (CLA+) cells of peripheral blood mononuclear cells from psoriasis patients compared with the expression in healthy individuals. This result showed that the infiltrated CLA+ T cells with the Vbeta13-DWTSGV-Jbeta2.7 motif in peripheral blood mononuclear cells from psoriasis patients might be involved in the development of psoriatic lesions. In addition, the results in this study suggest that the infiltrated T cells with the Vbeta13-DWTSGV-Jbeta2.7 motif in psoriatic lesions may be involved in the pathogenesis of psoriasis.

Special report. Steroid receptors in breast cancer.

Knowledge of the steroid receptor content of human breast cancer is important for proper diagnosis and for deciding the proper treatment for metastatic disease. Few patients whose breast cancers lack estrogen receptor will benefit from endocrine therapy, while more than half of patients with estrophilin-rich cancers will obtain objective remissions. The probability of objective response to endocrine therapy increases with an increase in the quantity of estrogen receptor in the cancer. Furthermore, patients whose cancers have both estrogen and progestin receptors have a better probability of response than patients whose lesions have only one of the receptors present, although even in such cases the response rate is higher than that seen in patients whose tumors lack both receptors. The data currently available suggest that receptor assays carried out on the primary tumor can be used for prediction of subsequent response to endocrine therapy, even at a later time of recurrent disease. Nonetheless, while sequential assays of receptors in lesions from the same patients are likely to be in agreement, when changes occur they tend to be reductions in amount of receptor or loss of receptor during disease progression . Breast cancer patients with receptor-positive tumors appear to have longer disease-free intervals and prolonged survival when compared with patients whose cancers lack ER, but clearly a part of the prolonged survival relates to response to endocrine therapies. Receptor positivity is frequently associated with well-differentiated tumors, while more poorly differentiated cancers, as well as medullary tumors, in general, and possibly cancers with significant lymphocytic infiltration, are more likely to be receptor negative. While there are some problems reproducing the exact quantitative receptor results among various laboratories assaying the same breast cancer, standard biochemical assays are still the only clinically proven and generally accepted procedure for assessing receptor status of a tumor. Histochemical assays based both on the steroid content of a tumor or using steroid-protein fluorescein complexes, while showing some correlation with standard biochemical assays for estrogen receptor, do not appear to detect receptor protein itself and can not be used instead of standard receptor assays. With the recent availability of monoclonal antibodies to the estrogen receptor, newer assays based on immunochemical procedures are under development and can be expected to provide simpler, less expensive, and more useful biochemical as well as immunohistochemical methods for receptor determination.(ABSTRACT TRUNCATED AT 400 WORDS)