| BMC Complementary and Alternative Medicine | |
| Immunological response in mice bearing LM3 breast tumor undergoing Pulchellin treatment | |
| Iracilda Zeppone Carlos1  Lucas Luis Colombo3  Marisa Campos Polesi Placeres2  Lucas Souza Ferreira2  Aline Tansini2  Lívia Carolina Abreu de Ribeiro2  Djamile Cordeiro de Matos2  | |
| [1] Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Rua Expedicionários do Brasil 1601, 14801-902, Araraquara, SP, Brazil;Laboratory of Clinical Immunology, School of Pharmaceutical Sciences, São Paulo State University, São Paulo, Brazil;Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina | |
| 关键词: Immune system; Cytokines; Breast cancer; Pulchellin; | |
| Others : 1232108 DOI : 10.1186/1472-6882-12-107 |
|
| received in 2012-03-29, accepted in 2012-07-11, 发布年份 2012 | |
PDF
|
|
【 摘 要 】
Background
Ribosome-inactivating proteins (RIP) have been studied in the search for toxins that could be used as immunotoxins for cancer treatment. Pulchellin, a type 2 RIP, is suggested to induce immune responses that have a role in controlling cancer.
Methods
The percentage of dendritic cells and CD4+ and CD8+ T cells in the spleen (flow cytometry), cytokines’ release by PECs and splenocytes (ELISA) and nitric oxide production by PECs (Griess assay) were determined from tumor-bearing mice injected intratumorally with 0.1 ml of pulchellin at 0.75 μg/kg of body weight. Statistical analysis was performed by one-way ANOVA with Tukey’s post hoc test.
Results
Pulchellin-treated mice showed significant immune system activation, characterized by increased release of IFN-γ and Th2 cytokines (IL-4 and IL-10), while IL-6 and TGF-β levels were decreased. There was also an increase in macrophage’s activation, as denoted by the higher percentage of macrophages expressing adhesion and costimulatory molecules (CD54 and CD80, respectively).
Conclusions
Our results suggest that pulchellin is promising as an adjuvant in breast cancer treatment.
【 授权许可】
2012 de Matos et al.; licensee BioMed Central Ltd.
【 预 览 】
| Files | Size | Format | View |
|---|---|---|---|
| 20151112153846676.pdf | 348KB | ||
| Figure 3. | 23KB | Image | |
| Figure 2. | 11KB | Image | |
| Figure 1. | 5KB | Image |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Van Ginderachte JA, Movahedi K, Ghassabeh GH, Meerschaut S, Beschin A, Raes G, De Baetselier P: Classical and alternative activation of mononuclear phagocytes: Picking the best of both worlds for tumor promotion. Immunobiology 2006, 211:487-501.
- [2]Goto LS, Castilho PV, Cominetti MR, Selistre-Araújo HS, Araújo APU: Endocytosis of pulchellin and its recombinant B-chain into K-562 cells: Binding and uptake studies. Biochim Biophys Acta 2007, 1770:1660-1666.
- [3]Stirpe F, Battelli MG: Ribossome-inactivating proteins: progress and problems. Cell Mol Life Sci 2006, 63:1850-1866.
- [4]Reyes LF, Nobre TM, Pavinatto FJ, Zaniquelli ME, Caseli L, Oliveira ON, Araújo AP: The role of the C-terminal region of pulchellin A-chain in the interaction with membrane model systems. Biochim Biophys Acta 2012, 1818:82-89.
- [5]Goto LS, Beltramini DI, de Moraes RA, de Araújo APU: Abrus pulchellus type-2 RIP, pulchellin: heterologous expression and refolding of the sugar-binding B chain. Protein Expr Purif 2003, 31:12-18.
- [6]Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR: Analysis of nitrate, nitrite, and [15 N] nitrate in biological fluids. Anal Biochem 1982, 126:131-138.
- [7]Fahmi T, Esendagli G, Yilmaz G, Kansu E, Guc D: Immune compartmentalization of T cell subsets in chemically-induced breast cancer. Scand J Immunol 2010, 72:339-348.
- [8]Chen ZK, Lin LW, Cai J, Yang FD, Cai HJ, Xue ES, Huang J, Wei HF, Zhang XJ: Effect of interstitial chemotherapy with ricin temperature-responsive gel for anti-breast cancer and immune regulation in rat. Chin J Integr Med 2011.
- [9]Chen J, Liu XS: Development and function of IL-10-IFN-γ-secreting CD4+ T cells. J Leukoc Biol 2009, 86:1305-1310.
- [10]Ramnath V, Kuttan G, Kuttan R: Effect of abrin on cell-mediated immune responses in mice. Immunopharmacol Immunotoxicol 2006, 28:259-268.
- [11]Biswas SK, Mantovani A: Macrophage plasticity and interaction with lymphocytes subsets: cáncer as a paradigm. Nat Immunol 2010, 11:889-896.
- [12]O'Garra A, Gabrysová L, Spits H: Quantitative events determine the differentiation and function of helper T cells. Nat Immunol 2011, 12:288-294.
- [13]Smith DC, Salio M, Lord JM, Roberts LM, Cerundolo V: Lack of dendritic cell maturation by the plant toxin ricin. Eur J Immunol 2004, 34:2149-2157.
- [14]Nicolini A, Carpi A, Rossi G: Cytokines in breast cancer. Cytokine Growth Factor Rev 2006, 17:325-337.
- [15]Drabsch Y, ten Dijke P: TGF-β signaling in breast cancer cell invasion and bone metastasis. J Mammary Gland Biol Neoplasia 2011, 16(2):97-108.
- [16]Su X, Ye J, Hsueh EC, Zhang Y, Hoft DF, Peng G: Tumor microenvironments direct the recruitment and expansion of human Th17 cells. J Immunol 2010, 184(3):1630-1641.
- [17]Wang J, Cai D, Ma B, Wu G, Wu J: Skewing the Balance of Regulatory T-cells and T-helper 17 Cells in Breast Cancer Patients. J Int Med Res 2011, 39(3):691-701.
- [18]Pukhal'skiĭ AL, Shmarina GV, Aleshkin VA: Regulatory T-cells: modern approaches to optimization of their numbers. Vestn Ross Akad Med Nauk 2011, 8:24-33.
- [19]Okada H, Kuwashima N: Gene therapy and biologic therapy with interleukin-4. Curr Gene Ther 2002, 2:437-450.
- [20]Mumm JB, Emmerich J, Zhang X, Chan I, Wu L, Mauze S, Blaisdell S, Basham B, Dai J, Grein J, Sheppard C, Hong K, Cutler C, Turner S, LaFace D, Kleinschek M, Judo M, Ayanoglu G, Langowski J, Gu D, Paporello B, Murphy E, Sriram V, Naravula S, Desai B, Medicherla S, Seghezzi W, McClanahan T, Cannon-Carlson S, Beebe AM, Oft M: IL-10 elicits IFNγ-dependent tumor immune surveillance. Cancer Cell 2011, 20:781-796.
PDF