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Regulation of interleukin-1 and tumor necrosis factor-alpha induced granulocyte-macrophage colony-stimulating factor gene expression: potential involvement of arachidonic acid metabolism.
Exp Hematol. 1994 Jan; 22(1):87-94.EH

Abstract

Signal transduction pathways evoked by interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) to stimulate expression of other cytokines in mesenchymal cells are not clearly understood. Stimulation of the murine bone marrow stromal cell line +/(+)-1.LDA 11 with IL-1 (500 U/ml) in combination with TNF-alpha (500 U/ml) (IL-1 plus TNF-alpha) induced expression of c-jun mRNA as well as granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA. We investigated the possibility that arachidonic acid metabolites, acting through protein kinase C (PKC) and perhaps also through the PKC-responsive transcription factor c-jun/AP-1, may be responsible for regulating GM-CSF transcription in these stromal cells. Expression of GM-CSF mRNA was preceded by IL-1 plus TNF-alpha induced arachidonate release (assayed using the 3H-derivative). Pretreatment of cells with the phospholipase A2 inhibitor quinacrine (20 microM) inhibited accumulation of both c-jun and GM-CSF mRNA but had no influence on expression of other genes induced by IL-1 and TNF-alpha, including leukemia inhibitory factor (LIF). In addition, quinacrine partially blocked IL-1 plus TNF-alpha induced 3H-arachidonic acid release from prelabeled stromal cells. Furthermore, exogenous arachidonate (10 to 50 microM) induced expression of c-jun. To investigate the role of arachidonate in GM-CSF transcription, we used a reporter vector consisting of the murine GM-CSF promoter linked to firefly luciferase. Transfection efficiency was monitored by assessing expression of a constitutively active gene, RSV-beta galactosidase. In this system, quinacrine significantly inhibited IL-1 plus TNF-alpha induced GM-CSF transcription assayed with the reporter construct. Exogenous arachidonic acid alone (10 microM) increased activity of GM-CSF reporter vector 1.5-fold over control. These results are consistent with the hypothesis that arachidonate metabolites are involved in the signaling pathway that leads to IL-1 plus TNF-alpha induced GM-CSF gene expression. Thus, transcriptional activation of GM-CSF gene is mediated, in part, by the arachidonate cascade.

Authors+Show Affiliations

Division of Hematology/Oncology, Indiana University School of Medicine, Walter Oncology Center, Indianapolis.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

8282065

Citation

Rizzo, M T., and H S. Boswell. "Regulation of Interleukin-1 and Tumor Necrosis Factor-alpha Induced Granulocyte-macrophage Colony-stimulating Factor Gene Expression: Potential Involvement of Arachidonic Acid Metabolism." Experimental Hematology, vol. 22, no. 1, 1994, pp. 87-94.
Rizzo MT, Boswell HS. Regulation of interleukin-1 and tumor necrosis factor-alpha induced granulocyte-macrophage colony-stimulating factor gene expression: potential involvement of arachidonic acid metabolism. Exp Hematol. 1994;22(1):87-94.
Rizzo, M. T., & Boswell, H. S. (1994). Regulation of interleukin-1 and tumor necrosis factor-alpha induced granulocyte-macrophage colony-stimulating factor gene expression: potential involvement of arachidonic acid metabolism. Experimental Hematology, 22(1), 87-94.
Rizzo MT, Boswell HS. Regulation of Interleukin-1 and Tumor Necrosis Factor-alpha Induced Granulocyte-macrophage Colony-stimulating Factor Gene Expression: Potential Involvement of Arachidonic Acid Metabolism. Exp Hematol. 1994;22(1):87-94. PubMed PMID: 8282065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of interleukin-1 and tumor necrosis factor-alpha induced granulocyte-macrophage colony-stimulating factor gene expression: potential involvement of arachidonic acid metabolism. AU - Rizzo,M T, AU - Boswell,H S, PY - 1994/1/1/pubmed PY - 1994/1/1/medline PY - 1994/1/1/entrez SP - 87 EP - 94 JF - Experimental hematology JO - Exp Hematol VL - 22 IS - 1 N2 - Signal transduction pathways evoked by interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) to stimulate expression of other cytokines in mesenchymal cells are not clearly understood. Stimulation of the murine bone marrow stromal cell line +/(+)-1.LDA 11 with IL-1 (500 U/ml) in combination with TNF-alpha (500 U/ml) (IL-1 plus TNF-alpha) induced expression of c-jun mRNA as well as granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA. We investigated the possibility that arachidonic acid metabolites, acting through protein kinase C (PKC) and perhaps also through the PKC-responsive transcription factor c-jun/AP-1, may be responsible for regulating GM-CSF transcription in these stromal cells. Expression of GM-CSF mRNA was preceded by IL-1 plus TNF-alpha induced arachidonate release (assayed using the 3H-derivative). Pretreatment of cells with the phospholipase A2 inhibitor quinacrine (20 microM) inhibited accumulation of both c-jun and GM-CSF mRNA but had no influence on expression of other genes induced by IL-1 and TNF-alpha, including leukemia inhibitory factor (LIF). In addition, quinacrine partially blocked IL-1 plus TNF-alpha induced 3H-arachidonic acid release from prelabeled stromal cells. Furthermore, exogenous arachidonate (10 to 50 microM) induced expression of c-jun. To investigate the role of arachidonate in GM-CSF transcription, we used a reporter vector consisting of the murine GM-CSF promoter linked to firefly luciferase. Transfection efficiency was monitored by assessing expression of a constitutively active gene, RSV-beta galactosidase. In this system, quinacrine significantly inhibited IL-1 plus TNF-alpha induced GM-CSF transcription assayed with the reporter construct. Exogenous arachidonic acid alone (10 microM) increased activity of GM-CSF reporter vector 1.5-fold over control. These results are consistent with the hypothesis that arachidonate metabolites are involved in the signaling pathway that leads to IL-1 plus TNF-alpha induced GM-CSF gene expression. Thus, transcriptional activation of GM-CSF gene is mediated, in part, by the arachidonate cascade. SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/8282065/Regulation_of_interleukin_1_and_tumor_necrosis_factor_alpha_induced_granulocyte_macrophage_colony_stimulating_factor_gene_expression:_potential_involvement_of_arachidonic_acid_metabolism_ L2 - https://antibodies.cancer.gov/detail/CPTC-FOS-4 DB - PRIME DP - Unbound Medicine ER -