Novel anti-inflammatory compounds from endophyte fungus in inhibitions of cytokine responses in macrophage RAW 264.7 cells

Wong, Shu Shyan, Finch, Sarah, Dalziel, Julie and Dunlop, James (2006). Novel anti-inflammatory compounds from endophyte fungus in inhibitions of cytokine responses in macrophage RAW 264.7 cells. In: Clinical Immunology. FOCIS 2006 Abstract Supplement - 6th Annual Meeting. FOCIS 2006, the 6th Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS), San Francisco, California, (S197-S197). 1-5 June 2006. doi:10.1016/j.clim.2006.04.538


Author Wong, Shu Shyan
Finch, Sarah
Dalziel, Julie
Dunlop, James
Title of paper Novel anti-inflammatory compounds from endophyte fungus in inhibitions of cytokine responses in macrophage RAW 264.7 cells
Conference name FOCIS 2006, the 6th Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS)
Conference location San Francisco, California
Conference dates 1-5 June 2006
Proceedings title Clinical Immunology. FOCIS 2006 Abstract Supplement - 6th Annual Meeting   Check publisher's open access policy
Journal name Clinical Immunology   Check publisher's open access policy
Place of Publication Orlando, Florida, U.S.A.
Publisher Academic Press
Publication Year 2006
DOI 10.1016/j.clim.2006.04.538
ISSN 1521-6616
1521-7035
Volume 119
Issue Supp. 1
Start page S197
End page S197
Total pages 1
Language eng
Abstract/Summary Cytokines are pivotal proteins in regulating the homeostasis of immune system. Up- or down-regulation of cytokine production indicates modulation of the immune system in response to the environment. Many diseases are caused by excessive production of inflammatory cytokines in local or systemic tissues or organs. Here, two indole diterpenes, lolitrem B, produced by endophyte fungus, and its isomer. 31-epilolitrem B, were used to investigate their effects on pro-inflammatory cytokine interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-a)responses in in vitro cultured murine macrophage RAW 264.7 cells. Our studies showed that both compounds have significant effects on inhibiting both IL-6 and TNF-a production at 24 hr in the presence of lipopolysaccharide (LPS) from the lowest concentration of 20 nm and up to 2 uM. In the absence of LPS, there were no significant increases in production of either cytokine. Statistical analysis showed that the effects we observed were not caused by the presence of the dimethyl sulfoxide used to dissolve both toxins. Paxilline, the precursor of lolitrems and known big conductance potassium channel activated (BK) blocker, also inhibited the cytokine responses but at a much higher concentration of 1 uM. Cell proliferation assays showed that the lolitrems alone did not inhibit the growth of the cells at concentrations as high as 1 uM. Cells treated with both toxins in the presence and absence of LPS did not undergo apoptosis with FACS analysis. This further demonstrated that inhibition was not through the apoptotic pathway, suggesting alternative cascades involved in the regulation of the anti-inflammatory response. The ability of these compounds to inhibit cytokine responses may have potential as immunotherapeutic drugs for inflammation diseases in the future.
Subjects 1107 Immunology
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes Published as Abstract Su.111.

 
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Created: Thu, 25 Feb 2010, 01:05:37 EST by Jon Swabey on behalf of Institute for Molecular Bioscience