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BACKGROUND: Vitiligo is a common pigmentary disorder. Studies on its pathogenesis extensively investigated melanocytes' abnormalities and few studies searched for keratinocytes' role in disease development. Liver X receptor-α (LXR-α) is a member of nuclear hormone receptors that acts as a transcription factor. Its target genes are the main regulators of melanocyte functions. AIM: The aim of this study is to investigate keratinocytes' role in vitiligo pathogenesis through immunohistochemical expression of LXR-α in lesional, perilesional, and distant nonlesional vitiligo skin. MATERIALS AND METHODS: This case-control study was carried out on 44 participants. These included 24 patients with vitiligo and 20 age- and sex-matched normal individuals as a control group. Biopsies, from cases, were taken from lesional, perilesional, and distant nonlesional areas. Evaluation was done using immunohistochemical technique. RESULTS: Keratinocyte LXR-α expression was upregulated in the lesional and perilesional skin (follicular and interfollicular epidermis) compared with control skin (P <0.001 for all). There was significant association between higher histoscore (H-score) in lesional epidermis (P <0.001) and in hair follicle (P =0.001) and the presence of angiogenesis. There was significant association between higher H-score in lesional epidermis and suprabasal vacuolization (P =0.02). No significant association was found between H-score or expression percentage and clinical data of selected cases. CONCLUSION: LXR-α upregulation is associated with keratinocyte damage in vitiligo lesional skin that leads to decreased keratinocyte-derived mediators and growth factors supporting the growth and/or melanization of surrounding melanocytes. Therefore, melanocyte function and survival are affected.
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INTRODUCTION: Acne Vulgaris (AV) is a common inflammatory disease of pilosebaceous units. Liver X Receptor-α (LXR-α) is a ligand activated transcription factor. It controls transcription of genes involved in lipid and fatty acid synthesis. Cyclo-oxygenase 2 (COX2) is a rate limiting enzyme in prostaglandin synthesis. It plays important role in inflammation. AIM: To evaluate the immunohistochemical expression of LXR-α and COX2 in acne vulgaris skin biopsies to explore their possible pathogenic role in this disease. MATERIALS AND METHODS: Sixty five subjects were included (45 cases with AV and 20 age and gender-matched healthy controls). Skin biopsies were taken from lesional and perilesional skin of cases and from site-matched areas of control subjects. The evaluation of LXR-α and COX2 was done using immunohistochemical technique. Data were collected, tabulated and statistically analysed using a personal computer with "(SPSS) version 11" program. Chi-square test was used to study the association between qualitative variables. Mann-Whitney test was used for comparison between quantitative variables. Student's t-test was used for comparison between two groups having quantitative variables. Spearman's coefficient was used to study the correlation between two different variables. Differences were considered statistically significant with p<0.05. RESULTS: COX2 was upregulated in lesional skin compared with peilesional and control skin both in epidermis and pilosebaceous units (p<0.001 for all). Higher epidermal COX2% was significantly associated with papulopustular acne (p=0.009) and higher acne score (p=0.018). Higher pilosebaceous units COX2% was significantly associated with papulopustular acne (p=0.04). LXR-α was upregulated in lesional skin compared with peilesional and control skin both in epidermis and pilosebaceous units (p<0.001 for all). Higher LXR-α % in epidermis and pilosebaceous units was significantly associated with papulopustular acne (p=0.01 for both) and higher acne score (p=0.03 for both). Significant positive correlation was detected between COX2% and LXR-α % in epidermis (p=0.001, r=0.87) and pilosebaceous units (p=0.001, r=0.65). CONCLUSION: Both LXR-α and COX-2 play a role in the pathogenesis of acne vulgaris through their effects on cellular proliferation, inflammation and lipid synthesis. Research for new therapeutic modalities based on their inhibition is needed. More understanding of the interaction between LXR-α, COX2 and acne lesions may lead to effective interference, possibly directed toward specific cell types or steps within inflammatory pathways.
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BACKGROUND: Cyclooxygenase-2 (Cox-2) is the inducible form of cyclooxygenase enzyme. Cox-2 is induced in numerous processes such as cellular growth, differentiation, inflammation and tumorogenesis. PURPOSE: Assessment of Cox-2 expression in chronic gastritis and gastric carcinoma. MATERIAL AND METHODS: Sixteen chronic gastritis (CG) and 43 gastric carcinoma cases were subjected to an immunohistochemical approach using anti Cox-2 antibody. RESULTS: All CG cases displayed positive epithelial Cox-2 expression with only 25% positivity for stromal expression. Eighty six percent of gastric carcinoma showed epithelial Cox-2 expression that was significantly correlated with lymph node involvement (p<0.01), advanced stage (p=0.01), high microvessel density (MVD) (p=0.0001), vascular invasion (p=0.002), perineural invasion (p=0.01) and low apoptotic count (p<0.0001). Stromal Cox-2 expression was seen in 79% of gastric carcinoma cases and was significantly associated with low apoptotic count (p=0.0007), vascular invasion (p=0.001) and high microvessel density (MVD) (p=0.0003). Only stromal Cox-2 expression was significantly higher in gastric carcinoma than chronic gastritis (p=0.0001). CONCLUSIONS: Cox-2 appears to be involved in gastric carcinoma progression as it promotes angiogenesis, suppresses apoptosis and facilitates invasion and metastasis. Double expression of Cox-2 in gastric carcinoma epithelium and stroma and significant association between them demonstrate a paracrine cross effect between stromal and malignant epithelium.
