Deacetylravidomycin M, a New Inhibitor of IL-4 Signal Transduction, Produced by Streptomyces sp. WK-6326. I. Taxonomy, Fermentation, Isolation and Biological Activities.

The Journal of Antibiotics
2001.0

Abstract

Streptomyces sp. WK-6326, a soil isolate, was found to produce an inhibitor of interleukin (IL)-4 signal transduction. Two structurally related compounds, a novel one designated deacetylravidomycin M and the known deacetylravidomycin, were isolated from the culture broth by solvent extraction, silica gel column chromatography and HPLC. Deacetylravidomycin M inhibited IL-4-induced CD23 expression in U937 cells without any cytotoxic effect, whereas deacetylravidomycin showed no inhibitory activity. Interleukin (IL)-4 is known to be a cytokine which plays a central role in the regulation of immune response1). Binding of IL-4 to its receptor on B cells leads to the activation of the janus kinase (JAK)-signal transducer and activator transcription 6 (STAT6) pathway2). In this pathway, the receptor associated JAK1 and 3 phosphorylates tyrosine residue of STAT6. Then STAT6 forms dimers, translocates to the nucleus, binds the specific elements in the promoters of target genes, and transcriptionally activates these genes. As a result, B cells raise expression of CD23 and class switching to IgE. Production of IgE causes the release of various chemical mediators such as histamine, leukotriene, prostaglandin and so on3). Therefore, inhibitors of IL-4 signal transduction are expected to prevent allergic diseases. During the course of our screening program for inhibitors of IL-4 signal transduction, we discovered and isolated a new ravidomycin-related compound, termed deacetylravidomycin M4), along with a known compound deacetylravidomycin5) in the culture broth of Streptomyces sp. WK-6326(Fig. 1). In this paper, the taxonomy of the producing strain, fermentation, isolation and biological properties of the deacetylravidomycins are described.

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