Association of MICA Alleles with Autoimmune Thyroid Disease in Korean Children

Background. Major histocompatibility complex class I chain-related gene A (MICA) is a ligand for the activating NKG2D receptor expressed on natural killer (NK) cells. We aimed to assess the association of MICA polymorphism with autoimmune thyroid disease (AITD) in Korean children. Methods. Eighty-one patients with AITD were recruited. We analyzed MICA polymorphisms by PCR-SSP and compared the results with those of 70 healthy controls. Results. In AITD, the allele frequencies of MICA*010 (OR=2.21; 95% CI, 1.30–3.76, P<0.003, Pc<0.042) were higher than those of controls. Patients who did not have thyroid-associated ophthalmopathy showed higher frequencies of MICA*010 (OR=2.99; 95% CI, 1.47–6.08, P<0.003, Pc<0.042) and lower frequencies of MICA*008 (OR=0.08; 95% CI, 0.01–0.62, P<0.001, Pc<0.014) compared to those of controls. HLA-B*46, which shows the strongest association with AITD compared with other HLA alleles, showed the strongest linkage disequilibrium with MICA*010. Analyses of the associations between MICA*010 and HLA-B*46 with AITD suggest an association of the MICA allele with AITD. Conclusions. Our results suggest that innate immunity might contribute to the pathogenesis of AITD

Oxidative Stress-Protective and Anti-Melanogenic Effects of Loliolide and Ethanol Extract from Fresh Water Green Algae, Prasiola japonica

Loliolide is a monoterpenoid hydroxylactone found in many algae, including fresh water green algae, Prasiola japonica. To date, loliolide and compounds in P. japonica have not been studied systematically with respect to skin pharmacology. In this study, we investigated oxidative stress-protective and anti-melanogenic effects of loliolide and P. japonica ethanol extract (Pj-EE), known to contain loliolide, in human keratinocyte (HaCaT) cells and mouse melanoma (B16F10) cells. Loliolide suppressed the transcription of genes encoding matrix metalloproteinases (MMPS), which were induced in HaCaT cells by hydrogen peroxide (H2O2) treatment. Loliolide and Pj-EE not only reduced the melanin secretion and content in B16F10 cells but also increased the expression of the antioxidant proteins nuclear factor (erythroid-derived 2)-like 2 (NRF2) and heme oxygenase-1 (HO-1) in HaCaT cells subjected to H2O2 treatment. Furthermore, loliolide and Pj-EE decreased expression of the anti-melanogenic protein microphthalmia-associated transcription factor (MITF) and tyrosinase in B16F10 cells subjected to &alpha;-melanocyte-stimulating hormone (&alpha;-MSH) treatment. Our findings demonstrate that loliolide and Pj-EE have antioxidant and anti-melanogenic effects on skin

The Triacylated ATP Binding Cluster Transporter Substrate-binding Lipoprotein of Staphylococcus aureus Functions as a Native Ligand for Toll-like Receptor 2*S⃞

Some synthetic lipopeptides, in addition to native lipoproteins derived from both Gram-negative bacteria and mycoplasmas, are known to activate TLR2 (Toll-like receptor 2). However, the native lipoproteins inherent to Gram-positive bacteria, which function as TLR2 ligands, have not been characterized. Here, we have purified a native lipoprotein to homogeneity from Staphylococcus aureus to study as a native TLR2 ligand. The purified 33-kDa lipoprotein was capable of stimulating TLR2 and was identified as a triacylated SitC lipoprotein, which belongs to a family of ATP binding cluster (ABC) transporter substrate-binding proteins. Analyses of the SitC-mediated production of cytokine using mouse peritoneal macrophages revealed that the SitC protein (3 nm) induced the production of tumor necrosis factor-α and interleukin-6. Moreover, analysis of knock-out mice showed that SitC required TLR2 and MyD88, but not TLR1 or TLR6, for the induction of cytokines. In addition to the S. aureus SitC lipoprotein, we purified two other native ABC transporter substrate-binding lipoproteins from Bacillus subtilis and Micrococcus luteus, which were both shown to stimulate TLR2. These results demonstrate that S. aureus SitC lipoprotein is triacylated and that the ABC transporter substrate-binding lipoproteins of Gram-positive bacteria function as native ligands for TLR2