TNF-alpha, IL-4 and IL-10 cytokines induces changes in HO-1 and HDC expression in cervical cancer cells
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1
Instituto Mexicano del Seguro Social, Mexico
Background
Chronic infection with human papilloma virus (HPV) has been associated as an important factor in generating cancer. E6 and E7 viral proteins are involved in cell transformation. Likewise tumor cells generate escape mechanisms as the expression of molecules that regulate the immune response. HDC and HO-1 exert anti-apoptotic functions. These enzymes may represent another mechanism of resistance in cervical cancer cells.
Objectives.
We analyzed the gene and protein expression of heme oxygenase (HO-1) and histidine decarboxylase (HDC) enzymes in HPV+ HeLa and SiHa cervical cancer cell lines and HPV- C33A cancer cells treated with TNF-α, I-4 and IL-10 cytokines.
Methods
HeLa, SiHa and C33A cervical cancer cells were treated with pro and anti-inflammatory cytokines; mRNA was extracted and analyzed expression of HO1 and HDC by real-time PCR. Protein expression was assessed by flow cytometry.
Results
Cytokines treatment induces a downregulation in HDC gene expression in HPV+ cancer cells in comparison with untreated tumor cells. In HeLa and SiHa cells this gene is downregulated whereas in C33A cancer cells we observed upregulation of HDC gene. In general HDC and HO-1 protein expression was reduced in cancer cells treated with pro and anti-inflammatory cytokines.
Conclusions
HDC and HO-1 protein expression is modified when the cells were treated with cytokines. In HeLa, SiHa and C33 cancer cells the expression of these enzymes is similar, however at the gene level the behavior is different between cancer cell lines, and this could be due to the presence of HPV infection in some cancer cells.
References
Moody, C. A. and L. A. Laimins (2010). "Human papillomavirus oncoproteins: pathways to transformation." Nat Rev Cancer 10(8): 550-560.
Kareva, I. and P. Hahnfeldt (2013). "The Emerging "Hallmarks" of Metabolic Reprogramming and Immune Evasion: Distinct or Linked?" Cancer Res
Gozzelino, R., et al. (2010). "Mechanisms of Cell Protection by Heme Oxygenase-1." Annual Review of Pharmacology and Toxicology 50(1): 323-354.
Ichikawa, A., et al. (2010). "Molecular biology of histidine decarboxylase and prostaglandin receptors." Proceedings of the Japan Academy, Series B 86(8): 848-866.
Keywords:
Heme-oxynenase 1,
Histidine Decarboxylase,
Cervical cancer cells,
tNF-alpha,
Anti-inflammatory cytokines
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Gomez-Lomeli
P,
Ortiz-Lazareno
PC,
Bravo-Cuellar
A,
Hernandez-Flores
G,
Dominguez-Rodriguez
JR,
Jave-Suarez
LF and
Aguilar-Lemarroy
A
(2013). TNF-alpha, IL-4 and IL-10 cytokines induces changes in HO-1 and HDC expression in cervical cancer cells.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00634
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Received:
11 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Pablo C Ortiz-Lazareno, Instituto Mexicano del Seguro Social, Guadalajara, Mexico, pablolazareno@gmail.com