Your browser doesn't support javascript.
loading
PGE2 induced miR365/IL-6/STAT3 signaling mediates dendritic cell dysfunction in cancer.
Pandey, Vipul K; Premkumar, Kavitha; Kundu, Priya; Shankar, Bhavani S.
Afiliación
  • Pandey VK; Immunology Section, Radiation Biology & Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Mumbai 400 085, India.
  • Premkumar K; Immunology Section, Radiation Biology & Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Mumbai 400 085, India.
  • Kundu P; Immunology Section, Radiation Biology & Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Mumbai 400 085, India.
  • Shankar BS; Immunology Section, Radiation Biology & Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Mumbai 400 085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400 094, India. Electronic address: bshankar@barc.gov.in.
Life Sci ; 350: 122751, 2024 Aug 01.
Article en En | MEDLINE | ID: mdl-38797363
ABSTRACT

AIM:

To understand the mechanism of prostaglandin E2 (PGE2)-mediated immunosuppression in dendritic cells (DCs). MAIN

METHODS:

In vivo experiments were conducted on 4T1 tumor bearing mice (TBM). In vitro experiments were performed in bone marrow-derived DCs (BMDCs), or spleen cells. Cytokines were monitored by ELISA/ELIspot. Gene expression was monitored by RT-PCR/flow cytometry. KEY

FINDINGS:

In silico, in vitro, and in vivo experiments in 4T1 TBM revealed that PGE2 induced IL-6/pSTAT3 signaling through EP4 receptors in DCs, resulting in their dysfunction. These effects were reversed by EP4 antibody neutralization, EP4 antagonist, and STAT3 inhibitory peptides. PGE2 induced IL-6 was regulated by miR-365, as its mimic inhibited PGE2 induced IL-6 and the inhibitor increased lL-6 levels in DC. Bio-informatic analysis in human mammary cancers also revealed a strong compared co-relation between PGE2 and IL-6 (Correlation AnalyzeR) (R = 0.94). Mice bearing PTGS-2 KD 4T1 tumors had decreased tumor burden, PGE2, EP4, IL-6, and pSTAT3 signaling, along with improved DCs and T cell functions. Treatment of mice with a cyclooxygenase-2 (COX-2) inhibitor or EP4 antagonist decreased tumor burden, and this effect of EP4 antagonist was abrogated upon in vivo depletion of CD11c cells, indicating the crucial role of PGE2 signaling in DCs in tumor progression.

SIGNIFICANCE:

In summary, our data highlights the importance of dendritic cells in mediating PGE2-mediated immunosuppression and the use of EP4 or STAT3 inhibitors or miR365 mimics can restore immunogenicity in cancer.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Dinoprostona / Transducción de Señal / Interleucina-6 / MicroARNs / Factor de Transcripción STAT3 Límite: Animals / Female / Humans Idioma: En Revista: Life Sci Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Dinoprostona / Transducción de Señal / Interleucina-6 / MicroARNs / Factor de Transcripción STAT3 Límite: Animals / Female / Humans Idioma: En Revista: Life Sci Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Países Bajos