PMID- 8039245
OWN - NLM
STAT- MEDLINE
DCOM- 19940824
LR  - 20131121
IS  - 0008-8749 (Print)
IS  - 0008-8749 (Linking)
VI  - 157
IP  - 1
DP  - 1994 Aug
TI  - Induction of multiple cytokine gene expression and IRF-1 mRNA by flavone acetic 
      acid in a murine macrophage cell line.
PG  - 211-22
AB  - Flavone-8-acetic (FAA) acid is a potential chemotherapeutic agent that has 
      demonstrated strong immunomodulatory activity in murine model systems. The 
      immunomodulatory activity of this drug in murine systems has been linked to its 
      ability to rapidly induce cytokine gene expression in vivo and in mouse 
      splenocytes ex vivo. We have now developed a tissue culture model for studying 
      the molecular basis of induction of cytokine expression by FAA. Using the mouse 
      macrophage cell line, ANA-1, we can demonstrate the direct induction of 
      interferon beta (IFN beta), interleukin-6 (IL-6), tumor necrosis factor-alpha 
      (TNF alpha), and interferon response factor-1 (IRF-1) mRNA expression following 
      treatment with FAA. Furthermore, the induction of the IFN beta mRNA can occur in 
      the absence of new protein synthesis. Nuclear run-on experiments indicate that at 
      least part of the induction of IFN beta, IL-6, and TNF alpha mRNA occurs at the 
      transcriptional level while the increase in IRF-1 mRNA appears largely 
      post-transcriptional or due to the production of IFN beta protein. Additionally, 
      experiments using agents that interfere with second messengers demonstrate that 
      activation of the protein kinase C pathway is possibly involved in FAA gene 
      induction. The use of this tissue culture model system should lead to a more 
      complete understanding of the mechanisms involved in FAA-induced gene expression 
      and help determine why this drug is inactive on human cells.
FAU - Eader, L A
AU  - Eader LA
AD  - Biological Carcinogenesis and Development Program, Program Resources, 
      Inc./DynCorp., Frederick, Maryland 21702-1201.
FAU - Gusella, L
AU  - Gusella L
FAU - Dorman, L
AU  - Dorman L
FAU - Young, H A
AU  - Young HA
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Cell Immunol
JT  - Cellular immunology
JID - 1246405
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Cytokines)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Flavonoids)
RN  - 0 (Interferon Regulatory Factor-1)
RN  - 0 (Irf1 protein, mouse)
RN  - 0 (Phosphoproteins)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 87626-55-9 (flavone acetic acid)
RN  - 98600C0908 (Cycloheximide)
SB  - IM
MH  - Adjuvants, Immunologic/antagonists & inhibitors/*pharmacology
MH  - Animals
MH  - Cell Line
MH  - Cycloheximide/pharmacology
MH  - Cytokines/*biosynthesis/genetics
MH  - DNA-Binding Proteins/*biosynthesis
MH  - Flavonoids/antagonists & inhibitors/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Interferon Regulatory Factor-1
MH  - Macrophages/*drug effects/immunology
MH  - Mice
MH  - Phosphoproteins/*biosynthesis
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - RNA, Messenger/drug effects
MH  - Transcriptional Activation
EDAT- 1994/08/01 00:00
MHDA- 1994/08/01 00:01
CRDT- 1994/08/01 00:00
PHST- 1994/08/01 00:00 [pubmed]
PHST- 1994/08/01 00:01 [medline]
PHST- 1994/08/01 00:00 [entrez]
AID - S0008-8749(84)71217-2 [pii]
AID - 10.1006/cimm.1994.1217 [doi]
PST - ppublish
SO  - Cell Immunol. 1994 Aug;157(1):211-22. doi: 10.1006/cimm.1994.1217.