The procyanidin trimer C1 induces macrophage activation via NF-κB and MAPK pathways, leading to Th1 polarization in murine splenocytes

Sung, Nak-Yun; Yang, Miso; Song, Du-Sup; Byun, Eui‐Baek; Kim, Jae‐Kyung; Park, Jong-Heum; Song, Beom‐Seok; Lee, Ju-Woon; Park, Sang‐Hyun; Park, Hyunjin; Byun, Myung‐Woo; Byun, Eui-Hong; Kim, Jae‐Hun

doi:10.1016/j.ejphar.2013.02.059

Cited by 23 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, it is conceivable that THP-1 cells that were pretreated with PMA already have an elevated level of NF-kB activity when treated with procyanidin B1 or C1, which may have resulted in a different outcome in their study. Most recently, Sung et al reported that C1 activates the NF-kB and MAPK pathways leading to production of inflammatory cytokines in mouse macrophages [11]. Similarly, our results clearly show that C1 reactivates latent HIV-1 proviruses in human T cells via a mechanism dependent on the NF-kB and MAPK pathways, although the cellular receptor mediating the C1-induced activation of these pathways is yet to be identified.…”

Section: Discussionsupporting

confidence: 69%

“…NMR studies revealed that the structure of Tc-1 is identical to a previously reported compound C1 [11] (Fig. 1A); thus, Tc-1 was designated as C1 hereafter.…”

Section: Screening Of Herbal Extractsmentioning

confidence: 98%

“…Because C1 was recently reported to activate NF-kB through phosphorylation of IkBa and translocation of RelA [11], we analyzed the role of NF-kB in the reactivation of the latent HIV-1 provirus by C1. For this purpose, Jurkat cells were transduced with two lentiviral vectors expressing firefly luciferase driven by an NF-kB-dependent promoter and an EF1a promoter-driven Renilla luciferase, and the resultant reporter cells were designated as JKR cells.…”

Section: Nf-kb Mediates the Procyanidin C1-induced Reactivation Of Hiv-1mentioning

confidence: 99%

“…C1 was reported to induce phosphorylation of ERK in mouse macrophages [11]. To assess the importance of the MAPK pathway in the C1-induced activation of the latent HIV-1 provirus in JLR2 cells, cells pretreated with the MEK inhibitor U0126 were stimulated with C1 or PMA, and the reporter luciferase activity was measured.…”

Section: The Mapk Pathway Is Involved In Procyanidin C1-induced Provimentioning

confidence: 99%

See 3 more Smart Citations

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus

Hori

Barnor

Huu

et al. 2015

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-κB and MAPK signaling pathways because either overexpression of a super-repressor form of IκBα or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-κB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs.

show abstract

Section: Discussionsupporting

confidence: 69%

“…NMR studies revealed that the structure of Tc-1 is identical to a previously reported compound C1 [11] (Fig. 1A); thus, Tc-1 was designated as C1 hereafter.…”

Section: Screening Of Herbal Extractsmentioning

confidence: 98%

Section: Nf-kb Mediates the Procyanidin C1-induced Reactivation Of Hiv-1mentioning

confidence: 99%

Section: The Mapk Pathway Is Involved In Procyanidin C1-induced Provimentioning

confidence: 99%

See 2 more Smart Citations

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus

Hori

Barnor

Huu

et al. 2015

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

show abstract

“…These data indicate that procyanidin B1 interferes with the activation of TLR4/MD-2 signaling pathways. These results are consistent with the previous studies showing reduced NF-jB mRNA expression with procyanidin B1 treatment [1,34]. Furthermore, co-treatment reduced phosphorylation of p38 MAPK, which represents one of the primary signaling pathways involved in LPS-induced cytokine production [35].…”

Section: Discussionsupporting

confidence: 95%

Anti-inflammatory effect of procyanidin B1 on LPS-treated THP1 cells via interaction with the TLR4–MD-2 heterodimer and p38 MAPK and NF-κB signaling

Xing

et al. 2015

Mol Cell Biochem

View full text Add to dashboard Cite

Anti-inflammatory effects of procyanidin B1 have been documented; however, the molecular mechanisms that are involved have not been fully elucidated. Molecular docking models were applied to evaluate the binding capacity of lipopolysaccharide (LPS) and procyanidin B1 with the toll-like receptor (TLR)4/myeloid differentiation factor (MD)-2 complex. LPS-induced production of the proinflammatory cytokine tumor necrosis factor (TNF)-α in a human monocyte cell line (THP1) was measured by ELISA. mRNA expression of MD-2, TLR4, TNF receptor-associated factor (TRAF)-6, and nuclear factor (NF)-κB was measured by real-time PCR with or without an 18-h co-treatment with procyanidin B1. In addition, protein expression of phosphorylated p38 mitogen-activated protein kinase (MAPK) and NF-κB was determined by Western blotting. Structural modeling studies identified Tyr296 in TLR4 and Ser120 in MD-2 as critical sites for hydrogen bonding with procyanidin B1, similar to the sites occupied by LPS. The production of TNF-α was significantly decreased by procyanidin B1 in LPS-treated THP1 cells (p < 0.05). Procyanidin B1 also significantly suppressed levels of phosphorylated p38 MAPK and NF-κB protein, as well as mRNA levels of MD-2, TRAF-6, and NF-κB (all p < 0.05). Procyanidin B1 can compete with LPS for binding to the TLR4-MD-2 heterodimer and suppress downstream activation of p38 MAPK and NF-κB signaling pathways.

show abstract

Grape seed proanthocyanidin extract ameliorates hepatic lipid accumulation and inflammation in grass carp (Ctenopharyngodon idella)

Qin

Yang

et al. 2020

Fish Physiol Biochem

View full text Add to dashboard Cite

The procyanidin trimer C1 induces macrophage activation via NF-κB and MAPK pathways, leading to Th1 polarization in murine splenocytes

Cited by 23 publications

References 36 publications

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus

Anti-inflammatory effect of procyanidin B1 on LPS-treated THP1 cells via interaction with the TLR4–MD-2 heterodimer and p38 MAPK and NF-κB signaling

Grape seed proanthocyanidin extract ameliorates hepatic lipid accumulation and inflammation in grass carp (Ctenopharyngodon idella)

Contact Info

Product

Resources

About