Activation of LPS-inducible genes by the antitumor agent 5,6-dimethylxanthenone-4-acetic acid in primary murine macrophages. Dissection of signaling pathways leading to gene induction and tyrosine phosphorylation - PubMed (original) (raw)
. 1994 Nov 15;153(10):4684-93.
Affiliations
- PMID: 7525711
Activation of LPS-inducible genes by the antitumor agent 5,6-dimethylxanthenone-4-acetic acid in primary murine macrophages. Dissection of signaling pathways leading to gene induction and tyrosine phosphorylation
P Y Perera et al. J Immunol. 1994.
Abstract
The synthetic flavone analogue 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA) has shown promise as an antitumor agent and is currently a candidate for clinical trials. Because 5,6-MeXAA has been shown in a murine macrophage and a human myelomonocytic cell line to induce TNF-alpha mRNA and to activate macrophages to become tumoricidal, actions that are shared with bacterial LPS, we sought to determine the level of LPS mimetic activity exhibited by this low m.w. macrophage-activating agent. To elucidate its mechanisms of action, the capacity to induce a panel of LPS-inducible genes was assessed. 5,6-MeXAA was found to induce a subset of LPS-inducible genes within the panel in both Lpsn and Lpsd primary murine macrophages. Of the six LPS-inducible genes examined, there was marked induction of IP-10, D8, and D3; low induction of TNF-alpha gene expression; and insignificant induction of TNFR-2 and IL-1 beta genes. 5,6-MeXAA was also found to be a potent inducer of IFNs in macrophages of both strains, and of increased expression of the genes that encode the IFN regulatory factors IRF-1, IRF-2, and ICSBP. In contrast with LPS, 5,6-MeXAA failed to induce significantly any of the 40- to 45-kDa tyrosine phosphoproteins induced by LPS. These data suggest that 5,6-MeXAA shares with LPS certain biochemical pathways that lead to gene induction and allow for the additional dissection of the relationship of tyrosine phosphorylation and the expression of specific genes.
Similar articles
- Dissection of LPS-induced signaling pathways in murine macrophages using LPS analogs, LPS mimetics, and agents unrelated to LPS.
Vogel SN, Manthey CL, Perera PY, Li ZY, Henricson BE. Vogel SN, et al. Prog Clin Biol Res. 1995;392:421-31. Prog Clin Biol Res. 1995. PMID: 8524949 - Endotoxin-induced early gene expression in C3H/HeJ (Lpsd) macrophages.
Manthey CL, Perera PY, Henricson BE, Hamilton TA, Qureshi N, Vogel SN. Manthey CL, et al. J Immunol. 1994 Sep 15;153(6):2653-63. J Immunol. 1994. PMID: 7521367 - Induction mechanism of a single gene molecule: stochastic or deterministic?
Ko MS. Ko MS. Bioessays. 1992 May;14(5):341-6. doi: 10.1002/bies.950140510. Bioessays. 1992. PMID: 1637366 Review.
Cited by
- Mini review: STING activation during non-alcoholic fatty liver disease.
Li H, Guo X, Aquino E, Wu C. Li H, et al. Front Nutr. 2023 Mar 1;10:1139339. doi: 10.3389/fnut.2023.1139339. eCollection 2023. Front Nutr. 2023. PMID: 36937350 Free PMC article. Review. - The STING agonist, DMXAA, reduces tumor vessels and enhances mesothelioma tumor antigen presentation yet blunts cytotoxic T cell function in a murine model.
Graham PT, Nowak AK, Cornwall SMJ, Larma I, Nelson DJ. Graham PT, et al. Front Immunol. 2022 Nov 18;13:969678. doi: 10.3389/fimmu.2022.969678. eCollection 2022. Front Immunol. 2022. PMID: 36466911 Free PMC article. - Intracellular Nucleic Acid Sensing Triggers Necroptosis through Synergistic Type I IFN and TNF Signaling.
Brault M, Olsen TM, Martinez J, Stetson DB, Oberst A. Brault M, et al. J Immunol. 2018 Apr 15;200(8):2748-2756. doi: 10.4049/jimmunol.1701492. Epub 2018 Mar 14. J Immunol. 2018. PMID: 29540580 Free PMC article. - Promising Targets for Cancer Immunotherapy: TLRs, RLRs, and STING-Mediated Innate Immune Pathways.
Li K, Qu S, Chen X, Wu Q, Shi M. Li K, et al. Int J Mol Sci. 2017 Feb 14;18(2):404. doi: 10.3390/ijms18020404. Int J Mol Sci. 2017. PMID: 28216575 Free PMC article. Review. - Characterization of a Novel Human-Specific STING Agonist that Elicits Antiviral Activity Against Emerging Alphaviruses.
Sali TM, Pryke KM, Abraham J, Liu A, Archer I, Broeckel R, Staverosky JA, Smith JL, Al-Shammari A, Amsler L, Sheridan K, Nilsen A, Streblow DN, DeFilippis VR. Sali TM, et al. PLoS Pathog. 2015 Dec 8;11(12):e1005324. doi: 10.1371/journal.ppat.1005324. eCollection 2015 Dec. PLoS Pathog. 2015. PMID: 26646986 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources