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2001). While mammalian neutral SMase is a membrane-bound protein, bacterial SMase is a secretory protein released from cells into the media (Titball 1993). In an in vitro study by Di Marzio et?al. (1999), ceramide reportedly increased in human keratinocytes cell line HaCat that was cocultured with sonicated cells of Streptococcus thermophilus. Ceramide levels in treated keratinocytes were reported to increase 50�C60-fold http://www.selleckchem.com/products/sch772984.html after 18?h with respect to the basal value while control group showed only 12�C14-fold increase in ceramide level. It has been suggested that the increased level of ceramide was attributed to SMase (>0��1?mU?ml?1) obtained from sonicated cells of Strep.?thermophilus (Di Marzio et?al. 1999). These results were then confirmed using in vivo test on 17 healthy Caucasian volunteers aged between 24 and 47?years. 0��5?g of cream containing sonicated Strep.?thermophilus was applied twice daily on the volar surface of the forearms while base cream (control) was applied to the contralateral forearm. Results from this randomized, double-blind, paired-comparison design showed that cream containing sonicated Strep.?thermophilus induced a very significant (P? http://www.selleckchem.com/products/Bortezomib.html of topical treatment (639?��?136��21?pmol ceramides per ��g protein) as compared to controls (136?��?25?pmol ceramides per ��g protein). An increase in ceramide content was reported in the stratum corneum of all subjects upon topical application of cream containing lysed Strep.?thermophilus as well as cream containing SMase (4?ng per 50?��l PBS per ml base cream) (Di Marzio et?al. 1999). The effects of the Strep.?thermophilus-containing cream on atopic dermatitis patients were further corroborated by Di Marzio et?al. (2003). Following observation from a clinical http://www.selleck.cn/products/gdc-0068.html trial, the authors reported an improvement in symptoms such as erythema, scaling and pruritus upon 2-week application of the cream in the forearms of 11 patients. We have recently documented that both acid and neutral SMase could be produced by strains of lactobacilli and bifidobacteria at concentrations sufficient to promote ceramide production in skin cells with the possibility to improve skin barrier properties (Lew et?al. 2012). Also, the production of SMase by lactobacilli can be enhanced via the supplementation of divalent metal ions into the growth medium, due to improved binding affinity between the SMase and sphingomyelin as well as improved interaction distances between the important catalytic residues Glu53 and His296 with phosphate head group of sphingomyelin (Fig.?2) (Lew and Liong 2012). Lipoteichoic acid (LTA) is a structural component of the cell walls of Gram-positive bacteria and plays a vital role in the growth and physiology of the bacteria. LTA has been reported as one of the immune-stimulating component of both pathogenic and nonpathogenic Gram-positive bacteria (Kim et?al. 2008).