title: The role of interleukin 10 in human papilloma virus infection and progression to cervical carcinoma.
abstract: Although Human Papillomavirus (HPV) exerts a vital influence on cervical carcinogenesis, other factors influence the development of a squamous intraepithelial lesion (SIL) that may or not progress to cervical cancer. Among several cytokines, Interleukin 10 (IL-10) stands out as an important anti-inflammatory factor, leading to immune system evasion through an immunosuppressive state. In the cervical microenvironment, during different stages of HPV infection, IL-10 production can be induced and maintained by different cell sources, including infected keratinocytes, some subsets of dendritic cells (DC), tumor associated macrophages (TAM), T regulatory cells (Treg) and tumor cells. Further, a wide range of effects can be exerted by IL-10 on different cell populations, such as inhibiting proinflammatory cytokine production, DCs differentiation, antigen presenting function and T-helper 1 (Th1) polarization. IL-10 is one of several cytokines involved in cancer development and sustenance, although its role in cancer is still controversial and poorly understood. However, cervical IL-10 levels tend to increase in parallel to SIL development and are even higher within cervical tumors. Accumulating data have shown that after HPV infection, IL-10 levels are enhanced as a result of HPV E2, E6 and E7 proteins action over IL-10 gene transcription, while IL-10 stimulates HPV E6 and E7 expression. Therefore, this interplay between HPV and IL-10 creates a vicious cycle that could favor an immunosuppressive microenvironment in the cervix, facilitating the progression of a simple HPV infection to SIL or cervical cancer.
authors.affiliation: Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, State University of Londrina, 86.057-970, Paraná, Brazil. Electronic address: nandabrandao@hotmail.com.
authors.forename: Fernanda Costa Brandão
authors.initials: FCB
authors.lastname: Berti
authors.affiliation: Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, State University of Londrina, 86.057-970, Paraná, Brazil. Electronic address: anapaulalombardi91@gmail.com.
authors.forename: Ana Paula Lombardi
authors.initials: APL
authors.lastname: Pereira
authors.affiliation: Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, State University of Londrina, 86.057-970, Paraná, Brazil. Electronic address: guilherme_cebinelli@hotmail.com.
authors.forename: Guilherme Cesar Martelossi
authors.initials: GCM
authors.lastname: Cebinelli
authors.affiliation: Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, State University of Londrina, 86.057-970, Paraná, Brazil. Electronic address: klebertrugilo@hotmail.com.
authors.forename: Kleber Paiva
authors.initials: KP
authors.lastname: Trugilo
authors.affiliation: Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, State University of Londrina, 86.057-970, Paraná, Brazil. Electronic address: karen.brajao@gmail.com.
authors.forename: Karen
authors.initials: K
authors.lastname: Brajão de Oliveira
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D002584:Cervix Uteri / Q000276:immunology / Q000821:virology; D004268:DNA-Binding Proteins / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D018450:Disease Progression; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015603:Keratinocytes / Q000276:immunology / Q000821:virology; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000276:immunology; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology
chemical_list: D004268:DNA-Binding Proteins; C508609:IL10 protein, human; D009856:Oncogene Proteins, Viral; C076036:oncogene protein E2, Human papillomavirus type 1; D016753:Interleukin-10
keywords: Cervical carcinoma; Human papillomavirus; Immune modulation; Interleukin 10; Squamous intraepithelial lesions