Ritu Aggarwal1, Sunayana Misra2, Charu Guleria2, Vanita Suri3, Navdeep Mangat2, Madhulika Sharma2, Raje Nijhawan4, Ranjana Minz2. 1. Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. Electronic address: ritu_immunopath@yahoo.co.in. 2. Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. 3. Department of Obstetrics and Gynecology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. 4. Department of Cytology and Gynecologic Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Abstract
OBJECTIVE: Human papillomavirus (HPV) is a proven etiological agent for cervical cancer However, not all HPV infections result in cervical cancer. The mechanisms of host immune system to prevent/control HPV infection remain poorly understood. Toll-like receptors (TLRs) are a system of innate immune defense. HPV has been demonstrated to modulate TLR expression and interfere in TLR signaling pathways, leading to persistent viral infection and carcinogenesis. The aim was to study the relative gene expression of TLRs in cervical squamous cell carcinoma (SCC). METHODS: Gene expression profile of TLRs 1 to 9 was examined in 30 cervical SCCs and an equal number of normal cervical tissue samples using a PCR array platform. Gene expression studies for TLRs 3 and 7 were validated by western blotting. RESULTS: HPV was detected in all cases and in none of the controls (p<0.0001). HPV16 was the preponderant (83.3%) subtype. A significant downregulation in the relative gene expression of TLR3 (p<0.0001), TLR4 (p<0.0005) and TLR5 (p<0.0001) was observed in cases. A significant upregulation for TLR1 was observed (p=0.006). Although TLRs 2, 7, 8 and 9 were upregulated and TLR6 was downregulated, it was not significant. The western blot performed with antibodies against TLRs 3 and 7 confirmed the findings of the gene expression studies. CONCLUSIONS: A significant downregulation in the gene expression of TLRs 3, 4 and 5 and upregulation of TLR1 was observed in cervical SCC as compared to controls. Study results evoke the proposition for investigating TLRs 3, 4 and 5 agonists for therapeutic exploration.
OBJECTIVE:Human papillomavirus (HPV) is a proven etiological agent for cervical cancer However, not all HPV infections result in cervical cancer. The mechanisms of host immune system to prevent/control HPV infection remain poorly understood. Toll-like receptors (TLRs) are a system of innate immune defense. HPV has been demonstrated to modulate TLR expression and interfere in TLR signaling pathways, leading to persistent viral infection and carcinogenesis. The aim was to study the relative gene expression of TLRs in cervical squamous cell carcinoma (SCC). METHODS: Gene expression profile of TLRs 1 to 9 was examined in 30 cervical SCCs and an equal number of normal cervical tissue samples using a PCR array platform. Gene expression studies for TLRs 3 and 7 were validated by western blotting. RESULTS:HPV was detected in all cases and in none of the controls (p<0.0001). HPV16 was the preponderant (83.3%) subtype. A significant downregulation in the relative gene expression of TLR3 (p<0.0001), TLR4 (p<0.0005) and TLR5 (p<0.0001) was observed in cases. A significant upregulation for TLR1 was observed (p=0.006). Although TLRs 2, 7, 8 and 9 were upregulated and TLR6 was downregulated, it was not significant. The western blot performed with antibodies against TLRs 3 and 7 confirmed the findings of the gene expression studies. CONCLUSIONS: A significant downregulation in the gene expression of TLRs 3, 4 and 5 and upregulation of TLR1 was observed in cervical SCC as compared to controls. Study results evoke the proposition for investigating TLRs 3, 4 and 5 agonists for therapeutic exploration.
Authors: Marconi Rego Barros; Talita Helena Araújo de Oliveira; Cristiane Moutinho Lagos de Melo; Aldo Venuti; Antonio Carlos de Freitas Journal: J Immunol Res Date: 2018-05-02 Impact factor: 4.818
Authors: Alan Messala A Britto; Livia R Goes; Aida Sivro; Cintia Policarpo; Ângela R Meirelles; Yara Furtado; Gutemberg Almeida; James Arthos; Claudia Cicala; Marcelo A Soares; Elizabeth S Machado; Ana Lúcia M Giannini Journal: Front Immunol Date: 2020-09-03 Impact factor: 7.561