ABSTRACT
The failure of fusion of nasal and maxillary processes results in cleft lip and palate (CLP), which is one of the most common birth defects. The morphopathogenesis of this pathology is multifactorial and still largely unclear. The aim of this study was to evaluate the presence of nestin, transcriptor factor SOX3 (Sox3) and homeobox protein DLX-4 (Dlx-4) in complete unilateral (CU) and complete bilateral (CB) CLP affected facial tissue. Oral mucosa tissue samples were obtained from 17 CUCLP and 13 CBCLP patients during surgical cleft correction and 6 unaffected control subjects. Obtained tissue sections were stained with hematoxylin and eosin and by immunohistochemistry for nestin, Sox3 and Dlx-4. The intensity of staining was graded semiquantitatively. Nestin-positive structures were detected in all CUCLP and CBCLP patients' tissue samples, varying from moderate number of nestin-positive structures to numerous. Sox3 immunoreactivity was more prominent in epithelial cells in both patient groups with frequently patchy distribution. Mainly moderate number of Dlx-4-positive cells was observed in most of tissue samples. Statistically significant moderate positive correlation was found between nestin and Sox3 factors in CUCLP patient group (Spearman's rank correlation coefficient = .517, P = .034). Increase of nestinpositive structures suggests its role in the regulation of the remodeling of tissue in both CUCLP and CBCLP affected tissue. Dominance of Sox3 positivity in cleft affected epithelium indicates its possible role in (compensatory) formation of defective oral epithelium of CUCLP and CBCLP patients. The reduced expression of Dlx-4 implicates its limited regulatory role on the craniofacial development in CUCLP and CBCLP affected tissue.
La falla en la fusión de los procesos nasal y maxilar son causante de la fisura labiopalatina (FLP), que es uno de los defectos congénitos más comunes. La morfopatogenia de esta patología es multifactorial y aún poco clara. El objetivo de este estudio fue evaluar la presencia de nestina, el factor transcriptor SOX3 (Sox3) y la proteína homeobox DLX-4 (Dlx-4) en todo el tejido facial afectado por FLP bilateral unilateral (FU) y bilateral completa (FB). Se obtuvieron muestras de tejido de mucosa oral de 17 pacientes FUFLP y 13 FBFLP durante la corrección quirúrgica de la fisura y de 6 sujetos de control no afectados. Las secciones de tejido obtenidas se tiñeron con hematoxilina y eosina y mediante inmunohistoquímica para nestina, Sox3 y Dlx-4. La intensidad de la tinción fue graduada semicuantitativamente. Se detectaron estructuras positivas para nestina en todas las muestras de tejido de pacientes FUFLP y FBFLP, variando desde un número moderado a numerosas estructuras positivas para nestina. La inmunorreactividad de Sox3 fue más prominente en las células epiteliales en ambos grupos de pacientes con distribución frecuentemente irregular. Se observó un número principalmente moderado de células Dlx-4-positivas en la mayoría de las muestras de tejido. Se encontró una correlación positiva moderada estadísticamente significativa entre los factores de nestina y Sox3 en el grupo de pacientes FUFLP (coeficiente de correlación de rangos de Spearman = 0,517, P = 0,034). El aumento de estructuras positivas para nestina sugiere su papel en la regulación de la remodelación de tejido, tanto en tejido afectado por FUFLP como FBFLP. La dominancia de la positividad de Sox3 en el epitelio afectado de la fisura, indica su posible papel en la formación (compensatoria) del epitelio oral defectuoso de pacientes FUFLP y FBFLP. La expresión reducida de Dlx-4 implica su función reguladora limitada en el desarrollo craneofacial en tejido afectado por FUFLP y FBFLP.
Subject(s)
Cleft Lip/metabolism , Cleft Palate/metabolism , Homeodomain Proteins/metabolism , SOXB1 Transcription Factors/metabolism , Nestin/metabolism , ImmunohistochemistryABSTRACT
Background: Psoriasis vulgaris is an infl ammatory skin condition characterized by dramatic biochemical and immunological changes. Aims: The aim of the study was to evaluate antimicrobial response, tissue degeneration reactions and distribution of infl ammatory cytokines in untreated psoriatic skin as well as the correlations between these factors and infl uence on the course of the disease. Methods: We evaluated skin samples obtained from routine punch biopsies in 40 patients with psoriasis vulgaris. All tissue specimens were examined by hematoxylin and eosin staining and immunohistochemistry for human beta defensin 2 (HBD-2), matrix metalloproteinase 2 (MMP-2), tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and IL-8. The staining intensity was semi-quantitatively graded. Results: Numerous keratinocytes, fibroblasts and macrophages expressed HBD-2 while the number of MMP-2-positive macrophages, fi broblasts and epitheliocytes varied. TNF-alpha-positive cells varied from a few to numerous in each microscopic fi eld. IL-6-positive cells varied from a few to abundant and IL-8-positive cells from numerous to abundant in each fi eld. Limitations: This study had a rather small patient number. Conclusions: Psoriatic skin shows a strong correlative increase in skin antimicrobial proteins and enzymes mediating tissue degeneration suggesting that the skin maintains compensatory mechanisms during persistent remodeling. While individual notable decrease in antimicrobial proteins was observed in some tissue samples, generally the increased human beta defensin associated with psoriasis is likely to be due to an altered immune status. TNF-alpha, IL-6 and IL-8 are common cytokines expressed in psoriatic skin plaques to maintain the infl ammatory cycle. HBD-2, MMP-2 and TNF-alpha positively correlate with the severity of psoriasis. Meanwhile, the expression of IL-8 signifi cantly decreases with clinically more severe psoriasis, perhaps making these factors candidate prognostic factors for psoriatic inflammation.
ABSTRACT
Aims: To evaluate the appearance and distribution of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2) and tissue inhibitor of metalloproteinase-4 (TIMP-4) in lesional skin biopsies of psoriasis patients. Study Design: Observational study. Place and Duration of Study: Institute of Anatomy and Anthropology and Department of Infectology and Dermatology, Rīga Stradiņš University, between September 2013 and June 2014. Methodology: We included 40 patients (31 men, 9 women; age range 18-70 years) with Psoriasis vulgaris, with present characteristic psoriatic eruptions in typical localization sites and no treatment received. Skin samples were obtained using routine punch biopsy method. 10 clinically healthy skin samples obtained during nevus excision procedure were used as control material. All tissue specimens were stained with hematoxylin and eosin and by immunohistochemistry for MMP- 2, TIMP-2 and TIMP-4. The intensity of staining was graded semiquantitatively. Spearman’s rank correlation coefficient was calculated. Results: In psoriasis patients numerous MMP-2-containing keratinocytes were found in epidermis, MMP-2 positive dermal fibroblasts and inflammatory cells varied from few to abundant. Few epidermal cells and moderate to numerous dermal cells contained TIMP-2. Moderate to numerous epidermal and dermal cells contained TIMP-4. Statistically significant strong positive correlation was found between MMP-2 in epidermis and dermis (Spearman’s rank correlation coefficient = .878, P = .000). Statistically significant moderate positive correlation was found between TIMP-2 and TIMP-4 in dermis (Spearman’s rank correlation coefficient = .639, P = .000) and between TIMP-2 in epidermis and dermis (Spearman’s rank correlation coefficient = .564, P = .000). Conclusion: TIMP-4 seems to be most important inhibitor of psoriatic skin degeneration, richly raised by MMP-2. Its moderate correlation with TIMP-2 proves involvement of other tissue inhibitors in the degeneration inhibition and gives evidence about possible patterning between the tissue inhibitors of metalloproteinases.