Cytokine Production Inhibitors Produced by a Fungus, Oidiodendron griseum.

Abstract

A series of diterpenes were isolated from the fermentation broth of a fungus, Oidiodendron griseum CL37215. The diterpenes were identified as LL-Z1271 a, LL-Z1271/, CJ-14,445, PR 1388, CJ-14,604 and a new diterpene, CJ-14,515. They inhibited both lipopolysaccharide-induced interleukin-lj8 and tumor necrosis factor-a production in human whole blood with IC50s of the range from 0.049 to 100 [IM. Cytokines are produced by a variety of different cell types and act on nearly every tissue and organ1-1. Among identified cytokines, interleukin-1/3 (IL-1/3) and tumor necrosis factor-a (TNF-a) share many properties of

LL-Z1271α: An Interleukin-1β Production Inhibitor

“…In a screening program designed to discover new inhibitors of cytokine production, we have discovered LL-Z1271␣ from the fungus Oidiodendron griseum CL37215 (15). Figure 2 shows the effect on IL-1␤ production, TNF-␣ production and leucine uptake in human whole blood at various concentrations of LL-Z1271␣.…”

“…LL-Z1271␣ was isolated from the fermentation broth of the fungus, Oidiodendron griseum CL37215, as described in the previous paper (15). Acetyl-Tyr-Val-Ala-Asp-amino-4-methylcoumarin) (Ac-Tyr-Val-Ala-Asp-AMC), a fluorescent substrate, was purchased from Peptide Institute, Inc., Osaka, Japan; caspase-1 inhibitor I was from Bachem AG (Bubendolf, Switzerland).…”

“…The procedures were reported in detail previously (15). Data are presented as means Ϯ SEM from three independent experiments.…”

“…We recently identified LL-Z1271␣ as a new type of IL-1␤ production inhibitor (Fig. 1) from the fermentation broth of a fungus, Oidiodendron griseum CL37215 (15). The mechanism of IL-1␤ production inhibition by LL-Z1271␣ has not been elucidated.…”

Hirsutane Sesquiterpenes from Cultures of the Basidiomycete Marasmiellus sp. BCC 22389

“…Marasmiellus is a relatively large genus composed of more than 400 described species/subspecies; however, there have been only a few reports on the chemical constituents from this genus: cis -caryophillane sesquiterpenes from fermentation broth of Marasmiellus troyanus [3], picolinic acid derivatives (CJ-14,877 and CJ-14,897; cytokine production inhibitors) from Marasmiellus sp. CL21624 [4], and benzoxepine derivatives from M. ramealis [5, 6]. As part of our research program on utilization of fungal sources in Thailand, bioassay and chemical profile-based screenings were performed in an effort to discover novel bioactive compounds with diverse chemical structures.…”