HPV-Mediated Resistance to TNF and TRAIL Is Characterized by Global Alterations in Apoptosis Regulatory Factors, Dysregulation of Death Receptors, and Induction of ROS/RNS

Tatiane Karen Cabeça; Alice De Mello Abreu; Rafael Andrette; Vanesca De Souza Lino; Mirian Galliote Morale; Francisco Aguayo; Lara Termini; Luisa Lina Villa; Ana Paula Lepique; Enrique Boccardo

doi:10.3390/ijms20010198

HPV-Mediated Resistance to TNF and TRAIL Is Characterized by Global Alterations in Apoptosis Regulatory Factors, Dysregulation of Death Receptors, and Induction of ROS/RNS

Título traducido de la contribución: La resistencia mediada por el VPH a TNF y TRAIL se caracteriza por alteraciones globales en los factores reguladores de la apoptosis, desregulación de los receptores de muerte e inducción de ROS/RNS.

Tatiane Karen Cabeça
, Alice De Mello Abreu
, Rafael Andrette
, Vanesca De Souza Lino
, Mirian Galliote Morale
, Francisco Aguayo
, Lara Termini
, Luisa Lina Villa
, Ana Paula Lepique
, Enrique Boccardo

Universidade de São Paulo
Universidad de Chile

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

23 Citas (Scopus)

Resumen

La infección persistente por el virus del papiloma humano de alto riesgo (VPH-AR) es el principal factor de riesgo para el desarrollo de cáncer cervical invasivo, aunque no es suficiente para causar cáncer cervical. Diversos factores ambientales y del huésped desempeñan un papel clave en la iniciación/progresión del cáncer, incluyendo citocinas y otros mediadores de la respuesta inmunitaria. En este estudio, caracterizamos la respuesta a la acción individual y combinada de las citocinas proinflamatorias factor de necrosis tumoral (TNF) y ligando inductor de apoptosis relacionado con TNF (TRAIL) en células transformadas por VPH y queratinocitos humanos que expresan ectópicamente las proteínas tempranas E6 y E7 de diferentes tipos de VPH. Demostramos que los queratinocitos que expresan proteínas tempranas de VPH exhibieron alteraciones globales en la expresión de proteínas involucradas en la regulación/ejecución de la apoptosis, incluyendo los receptores de TNF y TRAIL. Además, proporcionamos evidencia de que el receptor 1 de TNF (TNFR1) estaba regulado a la baja y podría estar retenido en el citoplasma de los queratinocitos que expresan oncoproteínas HPV16. Finalmente, el análisis de fluorescencia demostró que el tratamiento con citocinas indujo la producción y liberación de especies reactivas de oxígeno y nitrógeno (ROS/RNS) en células que expresan oncogenes del VPH. Las alteraciones en la producción de ROS/RNS y la expresión de factores reguladores de la apoptosis en respuesta a mediadores inflamatorios podrían favorecer la acumulación de alteraciones genéticas en las células infectadas por el VPH. En conjunto, nuestros resultados sugieren que estos eventos podrían contribuir a la progresión de las lesiones y la aparición del cáncer.

Título traducido de la contribución	La resistencia mediada por el VPH a TNF y TRAIL se caracteriza por alteraciones globales en los factores reguladores de la apoptosis, desregulación de los receptores de muerte e inducción de ROS/RNS.
Idioma original	Inglés
Número de artículo	198
Publicación	International Journal of Molecular Sciences
Volumen	20
N.º	1
DOI	https://doi.org/10.3390/ijms20010198
Estado	Publicada - 7 ene 2019
Publicado de forma externa	Sí

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

ODS 3: Salud y bienestar

Palabras clave

Apoptosis
VPH
ROS/RNS
TNF
TRAIL

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Cabeça, T. K., De Mello Abreu, A., Andrette, R., Lino, V. D. S., Galliote Morale, M., Aguayo, F., Termini, L., Villa, L. L., Lepique, A. P., & Boccardo, E. (2019). HPV-Mediated Resistance to TNF and TRAIL Is Characterized by Global Alterations in Apoptosis Regulatory Factors, Dysregulation of Death Receptors, and Induction of ROS/RNS. International Journal of Molecular Sciences, 20(1), Artículo 198. https://doi.org/10.3390/ijms20010198

@article{4d77accc298e4995b821c2b7510f9426,

title = "HPV-Mediated Resistance to TNF and TRAIL Is Characterized by Global Alterations in Apoptosis Regulatory Factors, Dysregulation of Death Receptors, and Induction of ROS/RNS",

abstract = "Persistent infection with high-risk human papilloma virus (HR-HPV) is the main risk factor for the development of invasive cervical cancer although is not sufficient to cause cervical cancer. Several host and environmental factors play a key role in cancer initiation/progression, including cytokines and other immune-response mediators. Here, we characterized the response to the individual and combined action of the pro-inflammatory cytokines tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL) on HPV-transformed cells and human keratinocytes ectopically expressing E6 and E7 early proteins from different HPV types. We showed that keratinocytes expressing HPV early proteins exhibited global alterations in the expression of proteins involved in apoptosis regulation/execution, including TNF and TRAIL receptors. Besides, we provided evidence that TNF receptor 1 (TNFR1) was down-regulated and may be retained in the cytoplasm of keratinocytes expressing HPV16 oncoproteins. Finally, fluorescence analysis demonstrated that cytokine treatment induced the production and release of reactive oxygen and nitrogen species (ROS/RNS) in cells expressing HPV oncogenes. Alterations in ROS/RNS production and apoptosis regulatory factors expression in response to inflammatory mediators may favor the accumulation of genetic alterations in HPV-infected cells. Altogether, our results suggested that these events may contribute to lesion progression and cancer onset. ",

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note = "Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

month = jan,

day = "7",

doi = "10.3390/ijms20010198",

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Cabeça, TK, De Mello Abreu, A, Andrette, R, Lino, VDS, Galliote Morale, M, Aguayo, F, Termini, L, Villa, LL, Lepique, AP & Boccardo, E 2019, 'HPV-Mediated Resistance to TNF and TRAIL Is Characterized by Global Alterations in Apoptosis Regulatory Factors, Dysregulation of Death Receptors, and Induction of ROS/RNS', International Journal of Molecular Sciences, vol. 20, n.º 1, 198. https://doi.org/10.3390/ijms20010198

HPV-Mediated Resistance to TNF and TRAIL Is Characterized by Global Alterations in Apoptosis Regulatory Factors, Dysregulation of Death Receptors, and Induction of ROS/RNS. / Cabeça, Tatiane Karen; De Mello Abreu, Alice; Andrette, Rafael et al.
En: International Journal of Molecular Sciences, Vol. 20, N.º 1, 198, 07.01.2019.

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

TY - JOUR

T1 - HPV-Mediated Resistance to TNF and TRAIL Is Characterized by Global Alterations in Apoptosis Regulatory Factors, Dysregulation of Death Receptors, and Induction of ROS/RNS

AU - Cabeça, Tatiane Karen

AU - De Mello Abreu, Alice

AU - Andrette, Rafael

AU - Lino, Vanesca De Souza

AU - Galliote Morale, Mirian

AU - Aguayo, Francisco

AU - Termini, Lara

AU - Villa, Luisa Lina

AU - Lepique, Ana Paula

AU - Boccardo, Enrique

PY - 2019/1/7

Y1 - 2019/1/7

N2 - Persistent infection with high-risk human papilloma virus (HR-HPV) is the main risk factor for the development of invasive cervical cancer although is not sufficient to cause cervical cancer. Several host and environmental factors play a key role in cancer initiation/progression, including cytokines and other immune-response mediators. Here, we characterized the response to the individual and combined action of the pro-inflammatory cytokines tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL) on HPV-transformed cells and human keratinocytes ectopically expressing E6 and E7 early proteins from different HPV types. We showed that keratinocytes expressing HPV early proteins exhibited global alterations in the expression of proteins involved in apoptosis regulation/execution, including TNF and TRAIL receptors. Besides, we provided evidence that TNF receptor 1 (TNFR1) was down-regulated and may be retained in the cytoplasm of keratinocytes expressing HPV16 oncoproteins. Finally, fluorescence analysis demonstrated that cytokine treatment induced the production and release of reactive oxygen and nitrogen species (ROS/RNS) in cells expressing HPV oncogenes. Alterations in ROS/RNS production and apoptosis regulatory factors expression in response to inflammatory mediators may favor the accumulation of genetic alterations in HPV-infected cells. Altogether, our results suggested that these events may contribute to lesion progression and cancer onset.

AB - Persistent infection with high-risk human papilloma virus (HR-HPV) is the main risk factor for the development of invasive cervical cancer although is not sufficient to cause cervical cancer. Several host and environmental factors play a key role in cancer initiation/progression, including cytokines and other immune-response mediators. Here, we characterized the response to the individual and combined action of the pro-inflammatory cytokines tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL) on HPV-transformed cells and human keratinocytes ectopically expressing E6 and E7 early proteins from different HPV types. We showed that keratinocytes expressing HPV early proteins exhibited global alterations in the expression of proteins involved in apoptosis regulation/execution, including TNF and TRAIL receptors. Besides, we provided evidence that TNF receptor 1 (TNFR1) was down-regulated and may be retained in the cytoplasm of keratinocytes expressing HPV16 oncoproteins. Finally, fluorescence analysis demonstrated that cytokine treatment induced the production and release of reactive oxygen and nitrogen species (ROS/RNS) in cells expressing HPV oncogenes. Alterations in ROS/RNS production and apoptosis regulatory factors expression in response to inflammatory mediators may favor the accumulation of genetic alterations in HPV-infected cells. Altogether, our results suggested that these events may contribute to lesion progression and cancer onset.

KW - Apoptosis

KW - VPH

KW - ROS/RNS

KW - TNF

KW - TRAIL

KW - Apoptosis

KW - HPV

KW - ROS/RNS

KW - TNF

KW - TRAIL

UR - https://www.scopus.com/pages/publications/85059795676

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DO - 10.3390/ijms20010198

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SN - 1661-6596

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JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

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