Cyclic di-GMP disodium is a cyclic dinucleotide signaling molecule synthesized by bacteria and is a STING agonist [1]. Cyclic di-GMP disodium induces increased CD4 receptor expression and causes cell cycle arrest [2-3]. Cyclic di-GMP disodium is often used in cancer research [4].
In Escherichia coli, Cyclic di-GMP disodium (7.5μM; 18-24h) rescues rLCN2-mediated inhibition of Escherichia coli growth [5]. In H508 cells, Cyclic di-GMP disodium (2-400μM; 72h) inhibits basal and growth factor-induced proliferation of human colon cancer [1]. In CD4+ T cells, Cyclic di-GMP disodium (3μg/mL, 10μg/mL; 24h) treatment of anti-CD3/CD28 stimulated wild-type T cells resulted in significant inhibition of proliferation and upregulation of CD80 expression [6]. In myeloid-derived suppressor cells (MDSCs), low doses of Cyclic di-GMP disodium (0.2μM; 24h) significantly increased IL12 production [7].
In mouse mastitis model, prophylactic pretreatment of mice with Cyclic di-GMP disodium (1mg/kg, 4.1mg/kg; sc; injected every 6 hours, twice in total) inhibits infection [8]. In a mouse bacterial pneumonia model, pretreatment of mice with Cyclic di-GMP disodium (2.5mg/kg; sc; injected every 12 hours, twice in total) induced a significant protective immune response against challenge with a virulent strain of Klebsiella pneumoniae [9]. In pertussis mouse model, injection of Cyclic di-GMP disodium (2.5mg/kg; nasal; single administration) can induce protective immune responses against Bordetella pertussis bacterial challenge [10].
References:
[1]. Karaolis DK, Cheng K, Lipsky M, et al. 3′, 5′-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor-stimulated human colon cancer cell proliferation. Biochemical and biophysical research communications. 2005 Apr 1; 329(1): 40-45.
[2]. Wang Z, Celis E. STING activator c-di-GMP enhances the anti-tumor effects of peptide vaccines in melanoma-bearing mice. Cancer Immunology, Immunotherapy. 2015 Aug; 64: 1057-1066.
[3]. JSteinberger O, Lapidot Z, Ben-Ishai Z, et al. Elevated expression of the CD4 receptor and cell cycle arrest are induced in Jurkat cells by treatment with the novel cyclic dinucleotide 3′, 5′-cyclic diguanylic acid. FEBS letters. 1999 Feb 5; 444(1): 125-129.
[4]. Jenal U, Reinders A, Lori C. Cyclic di-GMP: second messenger extraordinaire. Nature Reviews Microbiology. 2017 May; 15(5): 271-284.
[5]. Li W, Cui T, Hu L, et al. Cyclic diguanylate monophosphate directly binds to human siderocalin and inhibits its antibacterial activity. Nature Communications. 2015 Sep 22; 6(1): 8330.
[6]. Concepcion AR, Wagner LE, Zhu J, et al. The volume-regulated anion channel LRRC8C suppresses T cell function by regulating cyclic dinucleotide transport and STING–p53 signaling. Nature immunology. 2022 Feb; 23(2): 287-302.
[7]. Chandra D, Quispe-Tintaya W, Jahangir A, et al. STING ligand c-di-GMP improves cancer vaccination against metastatic breast cancer. Cancer immunology research. 2014 Sep 1; 2(9): 901-910.
[8]. Karaolis DK, Means TK, Yang D, et al. Bacterial c-di-GMP is an immunostimulatory molecule. The Journal of Immunology. 2007 Feb 15; 178(4): 2171-2181.
[9]. Karaolis DK, Newstead MW, Zeng X, et al. Cyclic di-GMP stimulates protective innate immunity in bacterial pneumonia. Infection and immunity. 2007 Oct; 75(10): 4942-4950.
[10]. Elahi S, Van Kessel J, Kiros TG, et al. c-di-GMP enhances protective innate immunity in a murine model of pertussis. PloS one. 2014 Oct 15; 9(10): e109778.
Cyclic di-GMP disodium是一种由细菌合成的环二核苷酸信号分子，是STING激动剂 [1]。Cyclic di-GMP disodium可诱导CD4受体表达增加，并导致细胞周期停滞 [2-3]。Cyclic di-GMP disodium常用于癌症研究 [4]。
在大肠杆菌中，Cyclic di-GMP disodium（7.5μM；18-24h）可挽救rLCN2介导的大肠杆菌生长抑制 [5]。在H508细胞中，Cyclic di-GMP disodium（2-400μM；72h）可抑制人结肠癌的基底细胞癌和生长因子诱导的增殖 [1]。在CD4+T细胞中，Cyclic di-GMP disodium（3μg/mL、10μg/mL；24h）处理抗CD3/CD28刺激的野生型T细胞，可显著抑制其增殖并上调CD80表达 [6]。在髓系抑制细胞（MDSC）中，低剂量Cyclic di-GMP disodium（0.2μM；24小时）可显著增加IL12的产生 [7]。
在小鼠乳腺炎模型中，用Cyclic di-GMP disodium（1mg/kg，4.1mg/kg；sc；每6小时注射一次，共两次）对小鼠进行预防性预处理可抑制感染 [8]。在小鼠细菌性肺炎模型中，预先用Cyclic di-GMP disodium（2.5mg/kg；sc；每12小时注射一次，共两次）对小鼠进行治疗，可诱导对肺炎克雷伯菌强毒株攻击的保护性免疫反应 [9]。在小鼠百日咳模型中，注射Cyclic di-GMP disodium（2.5mg/kg；鼻腔给药；单次给药）可诱导对百日咳博德特氏菌攻击的保护性免疫反应 [10]。