(S)-Tetrahydroisoquinoline Alkaloid Inhibits LPS-Induced Arachidonic Acid Release through Downregulation of cPLA2 Expression

Choi, Jong Min; Choi, Young Hwa; Kim, Seok Kyun; Ahn, Kyong Hoon; Won, Jong Hoon; Lim, Joo Hyuk; Jang, Young-Joo; Lee, Sungsook; Kim, Dal-Hyun; Kim, Dae Kyong

doi:10.1007/s10059-013-0078-x

Cited by 8 publications

(9 citation statements)

References 38 publications

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“…Interestingly, whereas inflammatory genes were increased in progenitor cells from R26STAT3C stopfl/fl CD4Cre, we saw a significant decrease in IFN-stimulated genes in response to SCFA treatment and an increase in Dusp1, a negative regulator of osteoclast differentiation and a primary mediator of the resolution of inflammation. [24][25] A comprehensive comparison across all our experimental groups of the most significant IFN-stimulated genes from our pathway analysis revealed a remarkable decrease in gene expression among SCFA-treated R26STAT3C stopfl/fl CD4Cre mice, similar to the levels seen in our control groups (Figure 4D). Our findings indicate that SCFAs could modulate osteoclastogenesis by diminishing inflammation through IFN-and STAT1-driven immune responses.…”

Section: Discussionsupporting

confidence: 64%

Mitigation of Osteoclast‐Mediated Arthritic Bone Remodeling By Short Chain Fatty Acids

Yang,

Mullins,

Lejeune

et al. 2024

Arthritis & Rheumatology

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ObjectiveTo study the effects of Short Chain Fatty Acids (SCFAs) on arthritic bone remodeling.MethodsWe treated a recently described preclinical murine model of psoriatic arthritis (PsA), R26STAT3Cstopfl/fl CD4Cre mice, with SCFA supplemented water. We also performed in vitro osteoclast differentiation assays in the presence of serum‐level SCFAs to evaluate the direct impact of these microbial metabolites on maturation and function of osteoclasts. We further characterized the molecular mechanism of SCFAs by transcriptional analysis.ResultsThe osteoporosis condition in R26STAT3Cstopfl/fl CD4Cre animals is attributed primarily to robust osteoclast differentiation driven by an expansion of osteoclast progenitor cells (OCPs), accompanied by an impaired osteoblast development. We show that SCFA supplementation can rescue the osteoporosis phenotype in this model of PsA. Our in vitro experiments revealed an inhibitory effect of the SCFAs on osteoclast differentiation, even at very low serum concentrations. This suppression of osteoclast differentiation enabled SCFAs to impede osteoporosis development in R26STAT3Cstopfl/fl CD4Cre mice. Further interrogation revealed that bone marrow derived OCPs from diseased mice expressed a higher level of SCFA receptors than that of control mice and that the progenitor cells in the bone marrow of SCFA‐treated mice presented a modified transcriptomic landscape, suggesting a direct impact of SCFAs on bone marrow progenitors in the context of osteoporosis.ConclusionWe demonstrated how gut microbiota‐derived SCFAs can regulate distal pathology, i.e., osteoporosis, and identified a potential therapeutic option for restoring bone density in rheumatic disease, further highlighting the critical role of the gut‐bone axis in these disorders.image

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Section: Discussionsupporting

confidence: 64%

Mitigation of Osteoclast‐Mediated Arthritic Bone Remodeling By Short Chain Fatty Acids

Yang,

Mullins,

Lejeune

et al. 2024

Arthritis & Rheumatology

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“…Besides, NF‐κB is proven to be an inflammatory central transcription factor activated by receptor for advanced glycation end product (RAGE) with S100A12 gene, and S100A12 was proven to activate the ERK pathway, showing the positive connection among them . Moreover, a previous study showed that inhibition of cPLA2 expression might be a novel target for sepsis, indicating that silencing S100A12 could also inhibit cPLA2 with the positive association . Consistently, S100A12 could activate and represent a variety of signal transduction pathways in combination with Ca 2+ .…”

Section: Discussionmentioning

confidence: 81%

Retracted: Effects of S100A12 gene silencing on serum levels of anti‐inflammatory/pro‐inflammatory cytokines in septic rats through the ERK signaling pathway

Wen

Han

Wang

et al. 2018

J of Cellular Biochemistry

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We explored the effect of S100A12 gene on serum levels of anti-inflammatory/pro-inflammatory cytokines in septic rats by activating the extracellular signal-regulated kinase (ERK) signaling pathway. A total of 180 specific pathogen-free (SPF) rats were purchased to establish cecal ligation and puncture (CLP) model. Rats were assigned into the sham, model, empty vector, S100A12 siRNA, epidermal growth factor (EGF), and S100A12 siRNA + EGF groups. The expressions of S100A12, ERK-1, ERK-2, cPLA2, and NF-κB in liver tissues of rats among six groups were detected by RT-qPCR and western blotting. ELISA was used to determine serum levels of IL-1β, IL-10, TNF-α, procalcitonin (PCT), and C-reactive protein (CRP). Pearson correlation analysis was conducted to measure correlations. Cell apoptosis of rats among six groups was detected by Tunel staining. The expressions of S100A12, ERK-1, ERK-2, cPLA2, and NF-κB decreased in the S100A12 siRNA group while increased in the EGF group compared with the model group. S100A12 mRNA expression was positively correlated with mRNA expressions of related genes in the ERK signaling pathway (ERK-1, ERK-2, cPLA2, and NF-κB) in the model and empty vector groups. Expressions of IL-1β, IL-6, TNF-α, PCT, and CRP in the EGF group were higher than those in the model group, but were lower than those in the S100A12 siRNA group. Compared with the model group, cell apoptosis decreased in the S100A12 siRNA group but that increased in the EGF group. We demonstrates that S100A12 gene silencing decreases serum levels of anti-inflammatory/pro-inflammatory cytokines in septic rats by inhibiting the ERK signaling pathway.

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“…Degradation of p53 relieves repression of cyclin B1 transcription, increasing levels of cyclin B1 (Innocente et al, 1999;Krause et al, 2000). In contrast, the direct interaction between BRCA1 and cyclin B1 can prevent its degradation and stabilize cyclin B1 proteins (Choi et al, 2018). Therefore, HPV oncoproteins and BRCA1 have similar effects, to maintain elevated levels of cyclin B1.…”

Section: Discussionmentioning

confidence: 99%

BRCA1 deficiency enhances the aggressiveness of breast cancer cells expressing HPV16 oncoproteins

Sangthong,

Thuwajit,

Jensen

et al. 2024

Biology of the Cell

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Background InformationThe precise etiology of breast cancer is not completely understood, although women with BRCA1 gene mutations have a significantly increased risk of developing the disease. In addition, sporadic breast cancer is frequently associated with decreased BRCA1 gene expression. Growing evidence of Human papillomaviruses (HPVs) infections in breast tumors has raised the possibility of the involvement of HPVs in the pathogenesis of breast cancer. We investigated whether the effects of HPV oncoproteins E6 and E7 were influenced by the expression levels of BRCA1. HPV16E6E7 (prototype or E6D25E/E7N29S Asian variant type) were stably expressed in MDA‐MB231 breast cancer cells, wild type for BRCA1, or with BRCA1 knocked down.ResultsExpression of HPV16E6E7 oncogenes did not affect BRCA1 levels and the abundance of HPV16E6E7 was not altered by BRCA1 knockdown. BRCA1 levels did not alter HPV16E6E7‐dependent degradation of G1‐S cell cycle proteins p53 and pRb. However, we found that the expression of G2‐M cell cycle protein cyclin B1 enhanced by HPV16E6E7 was impacted by BRCA1 levels. Especially, we found the correlation between BRCA1 and cyclin B1 expression and this was also confirmed in breast cancer samples from a Thai cohort. We further demonstrated that the combination of HPV oncoproteins and low levels of BRCA1 protein appears to enhance proliferation and invasion. Transactivation activities of HPV16E6E7 on genes regulating cell proliferation and invasion (TGF‐β and vimentin) were significantly increased in BRCA1‐deficient cells.ConclusionsOur results indicate that a deficiency of BRCA1 promotes the transactivation activity of HPV16E6E7 leading to increase of cell proliferation and invasion.SignificanceHPV infection appears to have the potential to enhance the aggressiveness of breast cancers, especially those deficient in BRCA1.

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(S)-Tetrahydroisoquinoline Alkaloid Inhibits LPS-Induced Arachidonic Acid Release through Downregulation of cPLA2 Expression

Cited by 8 publications

References 38 publications

Mitigation of Osteoclast‐Mediated Arthritic Bone Remodeling By Short Chain Fatty Acids

Mitigation of Osteoclast‐Mediated Arthritic Bone Remodeling By Short Chain Fatty Acids

Retracted: Effects of S100A12 gene silencing on serum levels of anti‐inflammatory/pro‐inflammatory cytokines in septic rats through the ERK signaling pathway

BRCA1 deficiency enhances the aggressiveness of breast cancer cells expressing HPV16 oncoproteins

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