The Mycobacterium avium subsp paratuberculosis fibronectin attachment protein, a toll-like receptor 4 agonist, enhances dendritic cell-based cancer vaccine potencyopen access
- Authors
- Noh, Kyung Tae; Shin, Sung Jae; Son, Kwang Hee; Jung, In Duk; Kang, Hyun Kyu; Lee, Su Jung; Lee, Eun Kyung; Shin, Yong Kyoo; You, Ji Chang; Park, Yeong-Min
- Issue Date
- May-2012
- Publisher
- KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
- Keywords
- dendritic cells; FAP-A protein; Mycobacterium avium; glycogen synthase kinase-3; toll-like receptor 4
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.44, no.5, pp 340 - 349
- Pages
- 10
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 44
- Number
- 5
- Start Page
- 340
- End Page
- 349
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/20311
- DOI
- 10.3858/emm.2012.44.5.038
- ISSN
- 1226-3613
2092-6413
- Abstract
- In this study, we showed the direct interaction between Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein (FAP) and toll-like receptor4 (TLR4) via co-localization and binding by using confocal microscopy and co-immunoprecipitation assays. FAP triggered the expression of pro- and anti-inflammatory cytokines in a TLR4-dependent manner. In addition, FAP-induced cytokine expression in bone marrow-derived dendritic cells (BMDCs) was modulated in part by glycogen synthase kinase-3 (GSK-3). FAP-induced expression of CD80, CD86, major histocompatibility complex (MHC) class I, and MHC class II in TLR4(+/+) BMDCs was not observed in TLR4(-/-) BMDCs. Furthermore, FAP induced DC-mediated CD8(+) T cell proliferation and cytotoxic T lymphocyte (CTL) activity, and suppressed tumor growth with DC-based tumor vaccination in EG7 thymoma murine model. Taken together, these results indicate that the TLR4 agonist, FAP, a potential immunoadjuvant for DC-based cancer vaccination, improves the DC-based immune response via the TLR4 signaling pathway.
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