Concentration levels of IL-10 and TNFαcytokines in patients with human papilloma virus (HPV) DNA+and DNA−cervical lesions

Ali, Katan Sabir; Ali, Hisham Y M; Jubrael, Jaladet M. S.

doi:10.3109/1547691x.2011.642419

Cited by 25 publications

(28 citation statements)

References 19 publications

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“…TNFα was added to each of the single cell cultures at a concentration of 1 ng/ml, which is similar to the concentration found in the tumor microenvironment (Elamin et al, 2008; Charles et al, 2009; Ali et al, 2012). At this concentration TNFα was sufficient to induce MMP-9, but did not induce cell death, as was estimated by the XTT assay (1.03 ± 0.04, 0.96 ± 0.02, and 0.99 ± 0.05 folds for A498, MCF-7, and U937 cells, respectively, relative to each of the non-stimulated cells).…”

Section: Resultsmentioning

confidence: 99%

Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN

Amit-Cohen¹,

Rahat²,

Rahat³

2013

Front. Physiol.

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Tumor macrophages are generally considered to be alternatively/M2 activated to induce secretion of pro-angiogenic factors such as VEGF and MMPs. EMMPRIN (CD147, basigin) is overexpressed in many tumor types, and has been shown to induce fibroblasts and endothelial cell expression of MMPs and VEGF. We first show that tumor cell interactions with macrophages resulted in increased expression of EMMPRIN and induction of MMP-9 and VEGF. Human A498 renal carcinoma or MCF-7 breast carcinoma cell lines were co-cultured with the U937 monocytic-like cell line in the presence of TNFα (1 ng/ml). Membranal EMMPRIN expression was increased in the co-cultures (by 3–4-folds, p < 0.01), as was the secretion of MMP-9 and VEGF (by 2–5-folds for both MMP-9 and VEGF, p < 0.01), relative to the single cultures with TNFα. Investigating the regulatory mechanisms, we show that EMMPRIN was post-translationally regulated by miR-146a, as no change was observed in the tumoral expression of EMMPRIN mRNA during co-culture, expression of miR-146a was increased and its neutralization by its antagomir inhibited EMMPRIN expression. The secretion of EMMPRIN was also enhanced (by 2–3-folds, p < 0.05, only in the A498 co-culture) via shedding off of the membranal protein by a serine protease that is yet to be identified, as demonstrated by the use of wide range protease inhibitors. Finally, soluble EMMPRIN enhanced monocytic secretion of MMP-9 and VEGF, as inhibition of its expression levels by neutralizing anti-EMMPRIN or siRNA in the tumor cells lead to subsequent decreased induction of these two pro-angiogenic proteins. These results reveal a mechanism whereby tumor cell-macrophage interactions promote angiogenesis via an EMMPRIN-mediated pathway.

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Section: Resultsmentioning

confidence: 99%

Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN

Amit-Cohen¹,

Rahat²,

Rahat³

2013

Front. Physiol.

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“…However biopsy is an invasive procedure and is particularly non-desirable in the younger women desirous of conserving menstrual and childbearing functions. Hence further studies were carried out by authors who have observed that the higher local or circulatory peripheral concentrations of some cytokines are indicative of a higher risk of progression from CIN 1 to CIN 2 or 3 and further to invasive cancer and metastasis (Adam et al, 1999;Fugimoto et al, 2000;Pardo-Govea et al, 2005;Bais et al, 2007;Sharma et al, 2007;Hong et al, 2010;Kemp et al, 2010;Ali et al, 2012;Mhatre et al, 2012;Peghini et al, 2012;Lazarenko et al, 2014). Souza et al (2013) recently demonstrated higher serum concentrations of IL-17, mean-pg/ml: 22.50 in HSIL vs 12.20 in LSIL, and of IL-22, mean pg/ml 168.2 vs 61.48, p<0.05 respectively.…”

Section: Cytokines As Markers Of High Risk Of Progression Of Cin Gradesmentioning

confidence: 99%

Role of Cytokines in Genesis, Progression and Prognosis of Cervical Cancer

Paradkar¹,

Joshi²,

Mertia³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Cytokine research is currently at the forefront in cancer research. Deciphering the functions of these multiple small molecules, discovered within the cell and in intercellular spaces, with their abundance and pleotrophism, was initially a great challenge. Advances in analytical chemistry and molecular biology have made it possible to unravel the pathophysiological functions of these polypeptides/proteins which are called interleukins, chemokines, monokines, lymphokines and growth factors. With more than 5 million women contracting cervical cancer every year this cancer is a major cause of mortality and morbidity the world over, particularly in the developing countries. In more than 95% of cases it is associated with human papilloma virus (HPV) infection which is persistent, particularly in those with a defective immune system. Although preventable, the mere magnitude of prevalence of HPV in the world population makes it a dominating current health hazard. The discovery of cytokine dysregulation in cervical cancer has spurted investigation into the possibility of using them as biomarkers in the early diagnosis of cases at high risk of developing cancer. Their critical role in carcinogenesis and progression of cervical cancer is now being revealed to a great extent. From diagnostics to prognosis, and now with a possible role in therapeutics and prevention of cervical cancer, the cytokines are being evaluated in all anticancer approaches. This review endeavours to capture the essence of the astonishing journey of cytokine research in cervical neoplasia.

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“…For example, TGF-β is produced by Treg, and its level has a positive correlation with lesion progression (36). IL-10 is another significant Treg-producing cytokine whose presence would decrease CD8 + T cell infiltration and increase the amount of intratumoral Foxp3 + Treg cells, a critical event for CIN lesion progression (44,45). There is also a notable interaction between IL-10 and HPV-induced lesion progression (46).…”

Section: Interplay Between Treg Cells and Hrhpv Infection Tregs (Cd4mentioning

confidence: 99%

Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer

et al. 2015

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Abstract. Human papillomavirus (HPV) is widely known as a cause of cervical intraepithelial neoplasia (CIN) and cervical cancer. The mechanisms involved have been studied by numerous studies. The integration of the virus genome into the host cells results in the abnormal regulation of cell cycle control. HPV can also induce immune evasion of the infected cells, which enable the virus to be undetectable for long periods of time. The induction of immunotolerance of the host's immune system by the persistent infection of HPV is one of the most important mechanisms for cervical lesions. The present review elaborates on the roles of several types of immune cells, such as macrophages and natural killer cells, which are classified as innate immune cells, and dendritic cells (DCs), cluster of differentiation (CD)4 + /CD8 + T cells and regulatory T cells, which are classified as adaptive immune cells. HPV infection could effect the differentiation of these immune cells in a unique way, resulting in the host's immune tolerance to the infection. The immune system modifications induced by HPV infection include tumor-associated macrophage differentiation, a compromised cellular immune response, an abnormal imbalance between type 1 T-helper cells (Th1) and Th2 cells, regulatory T cell infiltration, and downregulated DC activation and maturation. To date, numerous types of preventative vaccines have been created to slow down carcinogenesis. Immune response activation-based therapeutic vaccine is becoming more and more attractive for the treatment of HPV-associated diseases.

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Concentration levels of IL-10 and TNFαcytokines in patients with human papilloma virus (HPV) DNA⁺and DNA⁻cervical lesions

Cited by 25 publications

References 19 publications

Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN

Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN

Role of Cytokines in Genesis, Progression and Prognosis of Cervical Cancer

Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer

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