The procyanidin trimer C1 inhibits LPS-induced MAPK and NF-κB signaling through TLR4 in macrophages

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

doi:10.1016/j.intimp.2012.11.021

Cited by 73 publications

(46 citation statements)

References 38 publications

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“…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: 92%

“…Procyanidin B1 is the major procyanidin found in most commonly eaten fruits and fruit juices [2,[25][26][27] and produces anti-inflammatory effects in human monocytes [1,9,10]. The data presented here indicate that procyanidin B1 may mediate these effects by acting as a competitive antagonist against TLR4/MD-2 activation of MAPK and NF-jB signaling and production of TNF-a.…”

Section: Discussionmentioning

confidence: 66%

“…Procyanidins are polyphenolic flavonoids that are abundant in commonly eaten fruits and fruit juices, for which procyanidins B1, B2, C1, and C2 possess a wide range of physiologic activities [1][2][3][4]. The consumption of these and other bioactive food compounds has been suggested to have beneficial effects on inflammation-related diseases [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…Procyanidins B1-5 differ by the position and configuration of monomeric linkages [8], which can lead to different pharmacologic effects. Recently, procyanidin B1 was shown to regulate innate and adaptive immunity by inhibiting inducible nitric oxide production and release of the proinflammatory cytokines interleukin-6 and tumor necrosis factor (TNF)-a by macrophages treated with lipopolysaccharide (LPS) [1]. Procyanidin B1 can impair inflammatory response signaling in human monocytes by suppressing the LPS-induced production of reactive oxygen species, thereby attenuating the activity of the inhibitor of nuclear factor (NF)-jB kinase subunit b and extracellular signalregulated kinase [9].…”

Section: Introductionmentioning

confidence: 99%

“…Modulation of the TLR4/MD-2 signaling pathway is important to prevent hyperactivation of immune responses that could contribute to the pathogenesis of autoimmune, chronic inflammatory, and infectious diseases [18,19]. The TLR4 signaling pathway can be suppressed via inhibitory alternative splice variants of essential signaling components [20][21][22][23][24] that are recruited to the TLR4 complex and lead to early-phase activation of TNF receptor-associated factor (TRAF)6 and NF-jB, and subsequent expression of proinflammatory cytokines (TNF-a and interleukin-6) and monocyte chemotactic protein-1 [1,4].…”

Section: Introductionmentioning

confidence: 99%

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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

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

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Merlin functions as a critical regulator in Staphylococcus aureus‐induced osteomyelitis

Zhou

Chen

Min

et al. 2021

Journal Cellular Physiology

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Merlin is known as a tumor suppressor, while its role in osteomyelitis remains unclear. This study aimed to investigate the role of Merlin in Staphylococcus aureus‐induced osteomyelitis and its underlying mechanisms. S. aureus‐induced osteomyelitis mouse model was established in Merlinfl/flLyz2cre/+ and Merlinfl/flLyz2+/+ mice. Bone marrow–derived macrophages (BMDMs) were isolated and stimulated by lipopolysaccharide (LPS). Bioassays, including quantitative reverse transcription polymerase chain reaction (qRT‐PCR), Western blot analysis, and enzyme‐linked immunosorbent assays, were conducted to determine the levels of target genes or proteins. Immunoprecipitation was applied to determine the interactions between proteins. DCAF1fl/fl mice were further crossed with Lyz2‐Cre mice to establish myeloid cell conditional knockout mice (DCAF1fl/flLyz2cre/+). It was found that the level of Merlin was elevated in patients with osteomyelitis and S. aureus‐infected BMDMs. Merlin deficiency in macrophages suppressed the production of inflammatory cytokines and ameliorated the symptoms of osteomyelitis induced by S. aureus. Merlin deficiency in macrophages also suppressed the production of proinflammatory cytokines in BMDMs induced by LPS. The inhibitory effects of Merlin deficiency on the inflammatory response were associated with DDB1‐Cul4‐associated factor 1 (DCAF1). In summary, Merlin deficiency ameliorates S. aureus‐induced osteomyelitis through the regulation of DCAF1.

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Proinflammatory Pathways: The Modulation by Flavonoids

Ribeiro

Freitas

Lima

et al. 2015

Medicinal Research Reviews

110

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Inflammation is a natural, carefully orchestrated response of the organism to tissue damage, involving various signaling systems and the recruitment of inflammatory cells. These cells are stimulated to release a myriad of mediators that amplify the inflammatory response and recruit additional cells. These mediators present numerous redundancies of functions, allowing a broad and effective inflammatory response, but simultaneously make the understanding of inflammation pathways much difficult. The extent of the inflammatory response is usually self-limited, although it depends on the balance between the pro- and anti-inflammatory signals. When that equilibrium is dislocated, a more widespread inflammatory response may take place. Flavonoids have been shown to be possible alternatives to the traditionally molecules used as anti-inflammatory agents. In fact, the biological activities of flavonoids include the modulation of the diverse phases of inflammatory processes, from the gene transcription and expression to the inhibition of the enzymatic activities and the scavenging of the reactive species. In the present review, the inflammatory network is widely revised and the flavonoids' broad spectrum of action in many of the analyzed inflammatory pathways is revised. This kind of integrated revision is original in the field, providing the reader the simultaneous comprehension of the inflammatory process and the potential beneficial activities of flavonoids.

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The procyanidin trimer C1 inhibits LPS-induced MAPK and NF-κB signaling through TLR4 in macrophages

Cited by 73 publications

References 38 publications

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

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

Merlin functions as a critical regulator in Staphylococcus aureus‐induced osteomyelitis

Proinflammatory Pathways: The Modulation by Flavonoids

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