title: p38-targeted inhibition of interleukin-12 expression by ethanol extract from Cordyceps bassiana in lipopolysaccharide-activated macrophages.
abstract: Cordyceps species have been known as ethnopharmacologically valuable mushroom in Korea, China, and Japan. This plant has been reported to exhibit a variety of pharmacological activities such as antioxidative, anticancer, anti-inflammatory, antidiabetic, and antiobesity effects. Although numerous pharmacological potentials of Cordyceps spp. have been demonstrated, immunomodulatory effect of Cordyceps bassiana has not been published yet. To evaluate its immunomodulatory activity, macrophages activated by lipopolysaccharide (LPS) were employed and the production of interleukin-12 (IL-12) was explored in terms of understanding its molecular inhibitory mechanism. Seventy percent of ethanol extract from Cordyceps bassiana (Cb-EE) was able to suppress the expression of IL-12, a cytokine regulating interferon-γ (IFN-γ)-producing T helper type 1 (Th1) polarization response, at the transcriptional levels. The inhibitory effect of Cb-EE seemed to be due to activator protein-1 (AP-1) translocation inhibition, according to immunoblotting analysis with nuclear fraction and luciferase assay. In agreement with this, Cb-EE strongly suppressed the phosphorylation of p38, a prime signal to stimulate AP-1 translocation and IL-12 production, strongly suppressed by SB203580, a p38 inhibitor. Furthermore, this extract also suppressed IFN-γ production in both phytohemaglutinin A and LPS-activated splenocytes. Our results suggest that Cb-EE can be applied as a Th1 response regulatory herbal medicine.
authors.affiliation: School of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea.
authors.forename: Se Eun
authors.initials: SE
authors.lastname: Byeon
authors.forename: Jaehwi
authors.initials: J
authors.lastname: Lee
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Gi Ho
authors.initials: GH
authors.lastname: Sung
authors.forename: Tae Woong
authors.initials: TW
authors.lastname: Kim
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D032661:Cordyceps / Q000737:chemistry*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology; D000431:Ethanol; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000502:physiology; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D018664:Interleukin-12; D000431:Ethanol; D007371:Interferon-gamma; D008156:Luciferases; D048051:p38 Mitogen-Activated Protein Kinases