These results indicate that 20% vitamin E ointment suppresses contact dermatitis by stabilizing keratinocytes, concomitantly with novel, interesting properties.

Hepatitis C virus (HCV) infects B lymphocytes and induces mixed cryoglobulinemia and B cell non-Hodgkin's lymphoma. The molecular mechanism for the pathogenesis of HCV infection-mediated B cell disorders remains obscure. To identify the possible role for HCV nonstructural 5A (NS5A) protein in B cells, we generated the stable B cell lines expressing Myc-His tagged NS5A. Immunoprecipitation study in the presence or absence of pervanadate (PV) implied that NS5A was tyrosine phosphorylated by pervanadate (PV) treatment of the cells. Therefore we examined pull-down assay by using glutathione S-transferase (GST)-fusion proteins of various Src homology 2 (SH2) domains, which associates with phosphotyrosine within a specific amino acid sequence. The results showed that NS5A specifically bound to SH2 domain of Fyn from PV-treated B cells in addition to Src homology 3 (SH3) domain. Substitution of Arg176 to Lys in the SH2 domain of Fyn abrogated this interaction. Deletion mutational analysis demonstrated that N-terminal region of NS5A was not required for the interaction with the SH2 domain of Fyn. Tyr334 was identified as a tyrosine phosphorylation site in NS5A. Far-western analysis revealed that SH2 domain of Fyn directly bound to NS5A. Fyn and NS5A were colocalized in the lipid raft. These results suggest that NS5A directly binds to the SH2 domain of Fyn in a tyrosine phosphorylation-dependent manner. Lastly, we showed that the expression of NS5A in B cells increased phosphorylation of activation loop tyrosine in the kinase domain of Fyn. NS5A containing ligand for both SH2 and SH3 domains enhances an aberrant autophosphorylation and kinase activity of Fyn in B cells.

Tyrosine phosphorylation of adaptor protein c‐Abl‐Src homology 3 (SH3) domain‐binding protein‐2 (3BP2, also referred to SH3BP2) positively regulates the B‐cell antigen receptor (BCR)‐mediated signal transduction, leading to the activation of nuclear factor of activated T cells (NFAT). Here we showed the effect of the proline to arginine substitution of 3BP2 in which is the most common mutation in patients with cherubism (P418R) on B‐cell receptor signaling. Comparing to the wild type, overexpression of the mutant form of 3BP2 (3BP2‐P416R, corresponding to P418R in human protein) enhanced BCR‐mediated activation of NFAT. 3BP2‐P416R increased the signaling complex formation with Syk, phospholipase C‐γ2 (PLC‐γ2), and Vav1. In contrast, 3BP2‐P416R could not change the association with the negative regulator 14‐3‐3. Loss of the association mutant that was incapable to associate with 14‐3‐3 could not mimic BCR‐mediated NFAT activation in Syk‐deficient cells. Moreover, BCR‐mediated phosphorylation of extracellular signal regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) was not affected by P416R mutation. These results showed that P416R mutation of 3BP2 causes the gain of function in B cells by increasing the interaction with specific signaling molecules.

The palm fruit açaí is known to have potential health benefits due to its antioxidant scavenging capacities. Pretreatment of IgE-sensitized mouse primary cultured mast cells with açaí pulp resulted in the dramatic suppression of antigen-induced degranulation in a dose-dependent manner. Similarly, açaí suppressed IgE-mediated degranulation and transcription of the cytokine genes from a cultured mast cell line of rat basophilic leukemia (RBL)-2H3 cells. Açaí could selectively inhibit FcεRI signaling pathways. Furthermore, the FcεRI-mediated complementary signaling pathway was also suppressed by açaí. These results demonstrate that açaí is a potent inhibitor of IgE-mediated mast cell activation.

ABSTRACT-The effect of vitamin E on the modulation of keratinocytes was studied in rats. A 1°10 lauroylsarcosine (LS) ointment caused skin erythema with keratinocyte-damage. A 30% vitamin E ointment markedly alleviated this erythema and protected keratinocytes from cell damage. Vitamin E (100 pg/ml) was also effective on LS (7.5 pg/ml)-induced proliferative reduction of cultured keratinocytes. On the other hand, ointment containing superoxide dismutase (SOD) (99,000 U/g) decreased the LS-induced erythema, suggesting that superoxide anion (02) produced from keratinocytes play an important role in the skin irritation. Indeed, LS induced 02-production from cultured keratinocytes. The 02-was significantly reduced by vitamin E and SOD, although vitamin E had no effects on 02-production in a xanthine-xanthine oxidase system, unlike the effect observed with SOD. These results indicate that vitamin E is an inhibitor of keratinocyte-modulation.