Interleukin-1ß triggers matrix metalloprotease-3 expression through p65/RelA activation in melanoma cells.

Melanoma shows highly aggressive behavior (i.e., local invasion and metastasis). Matrix metalloprotease-3 (MMP-3), a zinc-dependent endopeptidase, degrades several extracellular substrates and contributes to local invasion by creating a microenvironment suitable for tumor development. Here, we report that interleukin-1ß (IL-1ß) triggers the MMP-3 expression in canine melanoma cells. The activity of MMP-3 in the culture supernatant was increased in IL-1ß-treated melanoma cells. IL-1ß time- and dose-dependently provoked the mRNA expression of MMP-3. IL-1ß induced the migration of melanoma cells; however, this migration was attenuated by UK356618, an MMP-3 inhibitor. When the cells were treated with the nuclear factor-κB (NF-κB) inhibitor TPCA-1, the inhibition of MMP-3 expression was observed. In IL-1ß-treated cells, the phosphorylation both of p65/RelA and p105 was detected, indicating NF-κB pathway activation. In p65/RelA-depleted melanoma cells, IL-1ß-mediated mRNA expression of MMP-3 was inhibited, whereas this reduction was not observed in p105-depleted cells. These findings suggest that MMP-3 expression in melanoma cells is regulated through IL-1ß-mediated p65/RelA activation, which is involved in melanoma cell migration.

Tpl2 contributes to IL-1ß-induced IL-8 expression via ERK1/2 activation in canine dermal fibroblasts.

In autoimmune diseases, fibroblasts produce and secrete various cytokines and act as sentinel immune cells during inflammatory states. However, the contribution of sentinel immune cells (i.e. dermal fibroblasts) in autoimmune diseases of the skin, such as atopic dermatitis, has been obscure. The pro-inflammatory cytokine interleukin 1ß (IL-1ß) induces the expression of chemokines, such as interleukin 8 (IL-8), in autoimmune diseases of the skin. IL-8 induces the activation and recruitment of innate immune cells such as neutrophils to the site of inflammation. IL-1ß-mediated induction of IL-8 expression is important for the pathogenesis of autoimmune diseases; however, the intracellular singling remains to be understood. To elucidate the mechanism of the onset of autoimmune diseases, we established a model for IL-1ß-induced dermatitis and investigated MAPK signaling pathways in IL-1ß-induced IL-8 expression. We also identified that a MAP3K Tpl2 acts as an upstream modulator of IL-1ß-induced ERK1/2 activation in dermal fibroblasts. We observed an increase in the expression of IL-8 mRNA and protein in cells treated with IL-1ß. ERK1/2 inhibitors significantly reduced IL-1ß-induced IL-8 expression, whereas the inhibitor for p38 MAPK or JNK had no effect. IL-1ß induced ERK1/2 phosphorylation, which was attenuated in the presence of an ERK1/2 inhibitor. IL-1ß failed to induce IL-8 expression in cells transfected with siRNA for ERK1, or ERK2. Notably, a Tpl2 inhibitor reduced IL-1ß-induced IL-8 expression and ERK1/2 phosphorylation. We confirmed that the silencing of Tpl2 in siRNA-transfected fibroblasts prevented both in IL-1ß-induced IL-8 expression and ERK1/2 phosphorylation. Taken together, our data indicate the importance of Tpl2 in the modulation of ERK1/2 signaling involved in the IL-1ß-induced development of autoimmune diseases affecting the dermal tissue, such as atopic dermatitis.

Efficacy of a self-management education program for people with type 2 diabetes: results of a 12 month trial.

AIM: Patient education that enhances one's self-management ability is of utmost importance for improving patient outcomes in chronic diseases. We developed a 12 month self-management education program for type 2 diabetes, based on a previous 6 month program, and examined its efficacy. METHODS: A randomized controlled trial was carried out on outpatients with type 2 diabetes from two hospitals who met the criteria and gave consent to participate. They were randomly divided into an intervention group that followed the program and a control group that followed usual clinical practise. The intervention group received <30 min of monthly interviews based on the program's textbook and biweekly telephone calls from a nurse educator throughout the 12 months. RESULTS: Of the 50 participants in the intervention group and the 25 participants in the control group, 42 and 23, respectively, completed the program (a completion rate of 84.0%). The body weight, HbA1c, self-efficacy, dietary and exercise stages, quality of life, diastolic blood pressure, and total cholesterol level were significant by two-way repeated-measures anova. As for changes over time within the groups, only the intervention group showed significant differences by Friedman's test. The complication prevention behaviors showed a high implementation rate in the intervention group. The overall evaluation of this program by the participants was very high and, therefore, they highly recognized the need for this type of program. CONCLUSIONS: Self-management education works successfully in relation to patients' behavior modification skills, degree of goal attainment, and self-efficacy, consequently improving their health outcomes.