Heat was found to increase tropoela

Heat was found to increase tropoelastin mRNA andprotein expression in the epidermis and in the dermis (Chenet al., 2005). Fibrillin-1 mRNA and protein expression wereincreased by heat in the epidermis but were diminished in thedermis (Chen et al., 2005). Therefore, the abnormal produc￾tion of tropoelastin and fibrillin by heat, like UV, in humanskin and their degradation by various MMPs, such as MMP￾12, may add to the accumulation of elastotic material inphotoaged skin (Chen et al., 2005).Heat induces angiogenesis in human skin in vivoIR radiation accounts for approximately 40% of the solarradiation energy reaching the earth’s surface, subsequentlygenerating heat and increasing skin temperature. Wedemonstrated that heat increases angiogenesis in human skinin vivo. The ratio of VEGF to TSP-1 and 2 is increased afterheat treatment, leading to increased angiogenesis (Kim et al.,2006a). Therefore, heat, in addition to UV, is an importantphysical stimulus for angiogenesis.Effects of heat on cytokine expression in human skinHeat can induce various cytokines in human skin. Toinvestigate the effects of heat treatment on TGF-b expression,human buttock skin was heated for 90 minutes at 431C. Theexpression of TGF-b1 and -b2 were increased at 24 hours,whereas that of TGF-b3 was decreased 24 hours after heattreatment (Seo and Chung, 2006). Heat treatment alsoincreased the expression of IL-6 and IL-12 mRNA signifi￾cantly in cultured dermal fibroblasts (Seo and Chung, 2006).Heat induces various cytokines, and these cytokines in turnregulate the extracellular matrix protein metabolism inhuman skin.Effects of heat on ROS productionThe transcriptional upregulation of MMPs can be mediatedby the increased production of reactive oxygen species(ROS). UV irradiation induces the formation of ROS incutaneous tissue (Kitazawa et al., 1997; Scharffetter-Kocha￾nek et al., 1997). ROS can be generated by many differentorganelles in response to various stimuli. Various enzymesystems including cyclooxygenase, nitric oxide synthase(NOS), xanthine oxidase, ribonucleotide reductase, mito￾chondrial electron transport systems, and NADPH oxidaseare involved in ROS production (Curtin et al., 2002). Like UV,heat shock generates H2O2 and O2K (Hall et al., 1994;Zhang et al., 2003). Heat shock-driven generation of ROSsubstantially affects the signaling pathways leading to MMP-1and MMP-9 induction. Heat shock generates H2O2 and O2Kthrough NADPH oxidase, xanthine oxidase, and the mito￾chondrial electron transport system in HaCaT cells (Shinet al., 2008). Heat shock-induced O2K is responsible forMMP-9 expression, whereas H2O2 is involved in theinduction of both MMP-1 and -9 (Shin et al., 2008).It has been demonstrated that topical application ofantioxidants, genistein or N-acetylcystein, can interrupt theUV-signaling cascade that leads to photoaging (Kang et al.,2003). These investigators demonstrated that UV increasesH2O2 in human skin in vivo and that both antioxidantsblocked UV-induced signaling. As heat is known to causeROS generation, we investigated the role of ROS in heat￾induced tropoelastin and fibrillin-1 expression (Chen et al.,2005). We found that pretreatment with N-acetylcystein orgenistein for 24 h prior to heat treatment inhibited the heat￾induced expression of tropoelastin in the epidermis, but notof fibrillin-1 (Chen et al., 2005). These results indicate thatheat-induced ROS may play a critical role in heat-inducedtropoelastin expression, but not in heat-induced fibrillin-1expression.Heat induces oxidative DNA damage in human skin in vivoUV radiation is absorbed directly by DNA and leads to theformation of pyrimidine dimers, of which more than 75% arethymine dimers (Patrick, 1977). UV radiation produces ROS.DNA is also susceptible to oxidative damage, and 8-oxo-dGis a useful biomarker of oxidative damage in DNA (Pelleet al., 2003). As heat shock in human skin can produce ROS,we investigated the effects of heat shock on DNA damage inhuman skin in vivo. Interestingly, heat shock at 431C for90 minutes, like UV irradiation, increased the 8-oxo-dG inthe epidermis and dermis of human skin in vivo maximally at24 hours post-heat (Figure 1a). However, heat shock, unlikeUV, did not produce thymidine dimer formation (Figure 1b).Therefore, heat-induced ROS induce cumulative DNAdamage through oxidative damage.The effects of IR and heat in the natural sunlight on human skinIn addition to UV radiation, IR plus visible light and the heatenergy generated by sunlight exposure induce MMP-1expression after exposing human skin to natural sunlight(Cho et al., 2008). IR plus visible light also increase MMP-9expression and decrease type I procollagen synthesis afterexposure to natural sunlight (Cho et al., 2008). Only UVradiation within natural sunlight results in neutrophil infiltra￾tion in human