TNF-• induces some proinflammatory cytokines including IL-1ß, IL-6, IL-8, and itself by activation of NF-κB or MAPKs (p38, JNK, ERK). These cytokines play important roles in various inflammatory skin diseases, such as psoriasis. Recently it was also reported that expression of cyclin E is upregulated by ERK pathway after TNF-• treatment. However, it was unknown whether curcumin, showing inhibitory effects on NF-κB and MAPKs, attenuates the expression of TNF-•induced IL-1ß, IL-6, IL-8, and TNF-• as well as cyclin E expression in HaCaT cells. In this study, we investigated the inhibitory effect of curcumin on expression of proinflammatory cytokines and cyclin E in TNF-•-treated HaCaT cells. We found that curcumin inhibited the expression of TNF-•-induced IL-1ß, IL-6, and TNF-•, but not IL-8, in TNF-•-treated HaCaT cells as well as the TNF-•-induced cyclin E expression. In addition, curcumin inhibited the activation of MAPKs (JNK, p38 MAPK, and ERK) and NF-κB in TNF-•-treated HaCaT cells. Taken together, curcumin exerts anti-inflammatory and growth inhibitory effects in TNF-•-treated HaCaT cells through inhibition of NF-κB and MAPK pathways.

The transforming growth factor-ß (TGF-ß) signaling pathway plays a key role in the abnormal accumulation of type I and III collagen of scleroderma. Activator protein-1 (AP-1) is a key regulatory protein in TGF-ß1-induced type I collagen synthesis. However, it is largely unknown whether AP-1 is involved in the cell proliferation of fibroblasts in scleroderma. In this study, we investigated the effects of the AP-1 oligo-deoxynucleotide (ODN) decoy on TGF-ß1induced cell growth in scleroderma fibroblasts. To investigate the inhibition of AP-1 ODN decoy on the growth rates of scleroderma fibroblasts through the regulation of cell cycle regulatory proteins, we transfected the AP-1 ODN decoy on scleroderma fibroblasts and analyzed the cell cycle regulatory proteins by RT-PCR and Western blot analysis. We found that the growth rates of normal fibroblasts and scleroderma fibroblasts showed similar rates. It is noteworthy that the scleroderma fibroblasts grew more rapidly than normal fibroblasts in the presence of TGF-ß1. Moreover, the transfection of AP-1 decoy ODN into scleroderma fibroblasts resulted in the down-regulation of the growth rates by the down-regulation of cyclin E. These results collectively suggest that AP-1 ODN decoy can down-regulate the growth rates of scleroderma fibroblasts, thus implying that AP-1 ODN decoy is a promising therapeutic tool for overcoming scleroderma.