Innate immune response adaptation in mice subjected to administration of DMBA and physical activity

Abdalla,Douglas R.; Aleixo,André Adriano Rocha; Murta,Eddie F.C.; Michelin,Márcia A.

doi:10.3892/ol.2013.1774

Innate immune response adaptation in mice subjected to administration of DMBA and physical activity

Authors:
- Douglas R. Abdalla
- André Adriano Rocha Aleixo
- Eddie F.C. Murta
- Márcia A. Michelin
View Affiliations

Affiliations: Oncology Research Institute, Federal University of the Triângulo Mineiro, Uberaba, Minas Gerais, CEP 38100‑000, Brazil, Discipline of Immunology, Federal University of the Triângulo Mineiro, Uberaba, Minas Gerais, CEP 38100‑000, Brazil
Published online on: December 24, 2013 https://doi.org/10.3892/ol.2013.1774
Pages: 886-890

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Although there is growing interest in studies that promote the benefits of exercise and the correlation between exercise and fighting cancer, previous studies have not been able to elucidate the underlying mechanisms. The aim of the present study was to investigate cytokine synthesis by peritoneal macrophages in the presence of mammary tumors and the effect of physical activity. Female BALB/c virgin mice (age, eight weeks) were obtained for the present study and divided into four groups: A no tumor/non‑trained control group; a no tumor/trained group subjected to swim training; a tumor/non‑trained group in which the mice received the carcinogenic drug, DMBA and a tumor/trained group in which the mice were subjected to DMBA and swim training protocols. Following the experimental period, immune cells were collected from the peritoneal fluid, placed in culture medium and stimulated with lipopolysaccharide. The presence of the cluster of differentiation‑14 marker and expression of the interleukin (IL)‑12 cytokine was assessed by flow cytometry and measured via an enzyme‑linked immunosorbent assay. The following cytokines were also identified: Interferon‑γ, IL‑4, IL‑10, IL‑12, tumor necrosis factor‑α and transforming growth factor‑β. Physical activity increased the quantity of IL‑12 producing macrophages, whereas the presence of a tumor decreased the quantity of macrophages expressing IL‑12. Tumor induction, in the absence of swim training, reduced macrophage‑profile 1 (M1) cytokine levels while increasing the presence of macrophage‑profile 2 cytokines. Physical activity in mice with tumors resulted in reductions in tumor development and promoted immune system polarization towards an antitumor M1 response pattern profile.

View Figures

View References

1	van Furth R, Cohn ZA, Hirsch JG, Humphrey JH, Spector WG and Langevoort HL: The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. Bull World Health Organ. 46:845–852. 1972.PubMed/NCBI
2	Mackaness GB: The immunological basis of acquired cellular resistance. J Exp Med. 120:105–120. 1964. View Article : Google Scholar : PubMed/NCBI
3	Gordon S and Taylor PR: Monocyte and macrophage heterogeneity. Nat Rev Immunol. 5:953–964. 2005. View Article : Google Scholar : PubMed/NCBI
4	Gordon S: The macrophage: past, present and future. Eur J Immunol. 37(Suppl 1): S9–S17. 2007. View Article : Google Scholar
5	Gordon S: Alternative activation of macrophages. Nat Rev Immunol. 3:23–35. 2003. View Article : Google Scholar
6	Martinez FO, Helming L and Gordon S: Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol. 27:451–483. 2009. View Article : Google Scholar : PubMed/NCBI
7	Mills CD, Kincaid K, Alt JM, Heilman MJ and Hill AM: M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol. 164:6166–6173. 2000. View Article : Google Scholar : PubMed/NCBI
8	Lefèvre L, Galès A, Olagnier D, Bernad J, Perez L, et al: PPARγ ligands switched high fat diet-induced macrophage M2b polarization toward M2a thereby improving intestinal Candida elimination. PLoS One. 5:e128282010.
9	Mantovani A, Bottazzi B, Colotta F, Sozzani S and Ruco L: The origin and function of tumor-associated macrophages. Immunol Today. 13:265–270. 1992. View Article : Google Scholar : PubMed/NCBI
10	Mantovani A, Schioppa T, Porta C, Allavena P and Sica A: Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev. 25:315–322. 2006. View Article : Google Scholar : PubMed/NCBI
11	Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG, et al: Macrophage polarization in tumour progression. Semin Cancer Biol. 18:349–355. 2008. View Article : Google Scholar : PubMed/NCBI
12	Dannenmann SR, Thielicke J, Stöckli M, Matter C, von Boehmr L, Cecconi V, Hermanns T, Hefermehl L, Schraml P, Moch H, et al: Tumor-associated macrophages subvert T-cell function and correlate with reduced survival in clear cell renal cell carcinoma. Oncoimmunology. 2:e235622013. View Article : Google Scholar : PubMed/NCBI
13	Woods JA: Exercise and resistance to neoplasia. Can J Physiol Pharmacol. 76:581–588. 1998. View Article : Google Scholar : PubMed/NCBI
14	Pedersen BK and Hoffman-Goetz L: Exercise and the immune system: regulation, integration, and adaptation. Physiol Rev. 80:1055–1081. 2000.PubMed/NCBI
15	Cassetta L, Cassol E and Poli G: Macrophage polarization in health and disease. ScientificWorldJournal. 11:2391–2402. 2011. View Article : Google Scholar : PubMed/NCBI
16	Zijlmans HJ, Fleuren GJ, Baelde HJ, Eilers PH, Kenter GG and Gorter A: Role of tumor-derived proinflammatory cytokines GM-CSF, TNF-alpha, and IL-12 in the migration and differentiation of antigen-presenting cells in cervical carcinoma. Cancer. 109:556–565. 2007. View Article : Google Scholar
17	Kizaki T, Takemasa T, Sakurai T, Izawa T, Hanawa T, Kamiya S, Haga S, Imaizumi K and Ohno H: Adaptation of macrophages to exercise training improves innate immunity. Biochem Biophys Res Commun. 372:152–156. 2008. View Article : Google Scholar : PubMed/NCBI
18	Lu Q, Ceddia MA, Price EA, Ye SM and Woods JA: Chronic exercise increases macrophage-mediated tumor cytolysis in young and old mice. Am J Physiol. 276:R482–R489. 1999.PubMed/NCBI
19	Woods J, Lu Q, Ceddia MA and Lowder T: Special feature for the Olympics: effects of exercise on the immune system: exercise-induced modulation of macrophage function. Immunol Cell Biol. 78:545–553. 2000. View Article : Google Scholar : PubMed/NCBI
20	Bombarda J, Melo JC, De Souza ER, Nóbrega OT and Córdova C: Exercise below the anaerobic threshold increases phagocytic and microbicide activities of neutrophils in Wistar rats. J Bras Patol Med Lab. 45:9–15. 2009.(In Portuguese).
21	Schmieder A, Michel J, Schönhaar K, Goerdt S and Schledzewski K: Differentiation and gene expression profile of tumor-associated macrophages. Semin Cancer Biol. 22:289–297. 2012. View Article : Google Scholar
22	Shirabe K, Mano Y, Muto J, Matono R, Motomura T, Toshima T, Takeishi K, Uchiyama H, Yoshizumi T, Taketomi A, et al: Role of tumor-associated macrophages in the progression of hepatocellular carcinoma. Surg Today. 42:1–7. 2012. View Article : Google Scholar : PubMed/NCBI
23	Abdalla DR, Murta EF and Michelin MA: The influence of physical activity on the profile of immune response cells and cytokine synthesis in mice with experimental breast tumors induced by 7,12-dimethylbenzanthracene. Eur J Cancer Prev. 22:251–258. 2013. View Article : Google Scholar