Chronic periodontitis (ChP) is a multifactorial disease influenced by microbial and host genetic variability; however, the role of beta-defensin-2 genomic (DEFB4) copy number (CN) variation (V) in ChP remains unknown. The association of the occurrence and severity of ChP and DEFB4 CNV was analyzed. Our study included 227 unrelated Caucasians, that is, 136 ChP patients (combined ChP) and 91 control individuals. The combined ChP group was subdivided into the severe ChP and slight-to-moderate ChP subgroups. To determine DEFB4 CNV, we isolated genomic DNA samples and analyzed them by relative quantitation using the comparative CT method. The serum beta-defensin-2 (hBD-2) level was determined via ELISA. The distribution pattern and mean DEFB4 CN did not differ significantly in combined ChP cases vs. the controls; however, the mean DEFB4 CN in the severe ChP group differed significantly from those for the control and slight-to-moderate ChP groups. Low DEFB4 CN increased the risk of severe ChP by about 3-fold. DEFB4 CN was inversely associated with average attachment loss. Mean serum hBD-2 levels were highest in the controls, followed by the slight-to-moderate ChP group and the severe ChP group. The results suggested an association between decreased DEFB4 CN and serum hBD-2 levels and periodontitis severity.

Dermatophytes initiate dermatophytosis, but susceptibility to infection is dictated by host genetic factors, although the role of some of these-such as human beta-defensin 2 (hBD-2) genomic (DEFB4) copy number (CN) variation and its induction by IL-22-remains unclear. This was investigated in this cross-sectional study in 442 unrelated Caucasian subjects, including 195 healthy controls and 247 dermatophytosis patients who were divided into five subgroups according to clinical presentation. DNA samples were evaluated for DEFB4 CN variation by relative quantification using the comparative CT method, and serum hBD-2 and IL-22 levels were determined by ELISA. DEFB4 CN in patients was significantly lower and, except in the tinea cruris subgroup, serum hBD-2 levels were higher than in controls. The positive correlation between hBD-2 levels and DEFB4 CN observed in controls was not detected in patients, who also had higher serum IL-22 levels that were positively correlated with hBD-2 levels. Moreover, unlike in control subjects, the serum IL-22 level was negatively correlated with DEFB4 CN in patients. Taken together, these findings suggest an association between decreased DEFB4 CN, elevated serum hBD-2 and IL-22 levels, and dermatophytosis, underscoring a gene/cytokine interaction in the occurrence of this infection.

ROS deleterious for the cells (Fig. 2d,e). TIEG1 protein expression was assessed at different time points after treatment, and expression levels calculated relative to untreated cells (Fig. 2e). NHF were particularly sensitive to stress induction, with a marked and prolonged decrease of TIEG1 expression shortly after H 2 O 2 , UVA and to a lesser extent with UVB treatment (Fig. 2e).Additional experiments can be found in supplementary data. ConclusionTIEG1 is a mediator of TGF-b pathway with an important function in bone tissue regulation (4). Here, we thoroughly described for the first time TIEG1 expression and regulation in human skin cells. We found that TIEG1 was well expressed in NHF and NHK at the mRNA and at the protein level both in primary cultures and in human skin biopsies. The function of TIEG1 as a TGF-b mediator was also revealed in human skin cells and therefore conserved from bone to skin tissues. TIEG1 expression was decreased after exogenous stress such as UV irradiation or H 2 O 2 treatment on primary cell cultures of NHF and NHK, and we found a correlation between in vivo skin photoexposure and low TIEG1 expression. Because TIEG1 is a positive mediator of TGF-b signalling, our results indicate that photoexposure lowers responsiveness to TGF-b pathway by decreasing TIEG1 expression. Previous reports suggest that UV irradiation blocks cellular responses to TGF-b primarily by downregulating its receptor expression (5,8). Here, we describe another mechanism by which stress can affect this multifunctional cytokine that regulates cell growth and differentiation.Our work suggests that TIEG1 might play an essential role for human skin both in dermis and epidermis although functional studies need to be performed in order to support this hypothesis. Acknowledgements Conflict of interestsNone. Supporting InformationAdditional supporting data may be found in the supplementary information of this article.Data S1. Materials and methods. Data S2. Results and discussion. Figure S1. Controls for TIEG1 protein detection. Figure S2. TIEG1 is induced by TGF-b in human skin cells. Figure S3. TIEG1 expression is not correlated to aging.