We examined the therapeutic effect of the extract from Sasa veitchii leaves (Sasa extract: SE) on the allergic skin inflammation model. SE derived from 0.141 g (low dose) or 0.562 g (high dose) of the leaves was administered orally for 15 days. High dose of SE suppressed ear swelling response induced by repeated 2,4-dinitrofluorobenzene (DNFB) paintings, and both low and high doses of SE reduced infiltration of immune cells into the ear dermis. Although the number of T cells, Treg, CD4 + T cells and CD8 + T cells in draining lymph nodes (dLNs) was not changed by SE, IFN-γ secretion from dLN induced by concanavalin A or 2,4-dinitrobenzenesulfonic acid was suppressed by a high dose of SE while IL-10 levels remained unchanged. These results suggest that SE suppresses allergic skin inflammation via reducing IFN-γ secreted from immune cells, especially T cells.
ARTICLE HISTORY
A novel hemorrhagic metalloproteinase, okinalysin, was isolated from the venom of Ovophis okinavensis. It possessed caseinolytic and hemorrhagic activities, and also hydrolyzed fibrinogen and collagen. These activities were inhibited by ethylenediaminetetraacetic acid (EDTA) but not by p-amidinophenyl methanesulfonyl fluoride hydrochloride (APMSF). The molecular mass of okinalysin was 22,202 Da measured by MALDI/TOF mass spectrometry. The primary structure of okinalysin was partially determined by Edman sequencing, and the putative zinc-binding domain HEXXHXXGXXH was found to be present in its structure. From these data, okinalysin is defined as a metalloproteinase belonging to a P-I class. The partial amino acid sequence of okinalysin was homologous to the C-terminus of MP 10, a putative metalloproteinase induced from transcriptome of the venom gland cDNA sequencing of O. okinavensis. Okinalysin possessed cytotoxic activity on cultured endothelial cells, and the EC50 on human pulmonary artery endothelial cells was determined to be 0.6 μg/mL. The histopathological study also showed that okinalysin causes the leakage of red blood cells and neutrophil infiltration. These results indicate that destruction of blood vessels by okinalysin is one of the main causes of hemorrhage.
Three synthetic peptides, EEYEYE (peptide 1), EEYEYEEEYEYE (peptide 2), and YEEEEY (peptide 3), were tested for their ability to induce common Id that had been previously characterized for murine antibodies specific to random synthetic polymers of glutamic acid, alanine, and tyrosine ((Glu,Ala,Tyr)n) (cGAT Id). Protein conjugates of either peptide 2 or peptide 3, but not peptide 1, induced cGAT Id. This unique approach directly identified two peptides capable of inducing cGAT Id antibodies. Previous immunization with peptide 1-protein conjugate inhibited the cGAT Id response to peptide 2 conjugated to a different protein carrier. Thus, a neighboring or overlapping epitope can be used to inhibit a cGAT Id-inducing epitope without the participation of carrier-specific Ts and without using anti-Id antibodies. In contrast, previous immunization with peptide 1-protein conjugate did not inhibit cGAT Id induction by peptide 3-protein conjugate or by (Glu,Ala,Tyr)n. This ruled out the participation of Id-specific Ts cells. The effectiveness of inhibition coincided with the avid binding of anti-peptide 1 antibodies to peptide 2, which was > 10 and 100 times stronger than the binding to peptide 3 and (Glu,Ala,Tyr)n, respectively. We hypothesize that the primed peptide 1-specific B cells capture and process peptide 2-protein efficiently and act as APC to Th cells specific to the protein of the challenging Ag, resulting in the selective and dominant activation of peptide 1-specific B cells. Thus, our data suggest that epitope priming can inhibit an Id response to a neighboring epitope by a mechanism of clonal dominance.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.