Ibuprofen treatment ameliorates memory deficits in rats with collagen-induced arthritis by normalizing aberrant MAPK/NF-κB and glutamatergic pathways

Zhang, Nai-You; Wang, Ting‐Hsuan; Chou, Ching-Hsuan; Wu, Kuo-Chen; Yang, Congrong; Kung, Fan-Lu; Lin, Chien-Ching

doi:10.1016/j.ejphar.2022.175256

Cited by 5 publications

(3 citation statements)

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“…5c ). Previous studies have reported that anti-inflammatory agent ibuprofen showed inhibitory effect on nuclear transcription factor-kappa B (NF-κB) 44 , 45 , and knockout of p50 (NF-κB subunit) reduced the expression of Irg1 in BMDMs 46 . To investigate the relationship between NF-κB (p50) and Irg1 , we treated BMDMs with ibuprofen and found attenuated binding activity of p50 to the promoter of the Irg1 gene by ChIP‒PCR (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Itaconate promotes hepatocellular carcinoma progression by epigenetic induction of CD8+ T-cell exhaustion

Gu,

Wei,

Suo

et al. 2023

Nat Commun

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Itaconate is a well-known immunomodulatory metabolite; however, its role in hepatocellular carcinoma (HCC) remains unclear. Here, we find that macrophage-derived itaconate promotes HCC by epigenetic induction of Eomesodermin (EOMES)-mediated CD8+ T-cell exhaustion. Our results show that the knockout of immune-responsive gene 1 (IRG1), responsible for itaconate production, suppresses HCC progression. Irg1 knockout leads to a decreased proportion of PD-1+ and TIM-3+ CD8+ T cells. Deletion or adoptive transfer of CD8+ T cells shows that IRG1-promoted tumorigenesis depends on CD8+ T-cell exhaustion. Mechanistically, itaconate upregulates PD-1 and TIM-3 expression levels by promoting succinate-dependent H3K4me3 of the Eomes promoter. Finally, ibuprofen is found to inhibit HCC progression by targeting IRG1/itaconate-dependent tumor immunoevasion, and high IRG1 expression in macrophages predicts poor prognosis in HCC patients. Taken together, our results uncover an epigenetic link between itaconate and HCC and suggest that targeting IRG1 or itaconate might be a promising strategy for HCC treatment.

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Section: Resultsmentioning

confidence: 99%

Itaconate promotes hepatocellular carcinoma progression by epigenetic induction of CD8+ T-cell exhaustion

Gu,

Wei,

Suo

et al. 2023

Nat Commun

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“…Moreover, epidemiological studies also showed an association between periodontitis and dementia ( 40 , 64 , 65 ). A previous study reported that non-steroidal anti-inflammatory drugs (NSAIDs) reduced the risk of dementia in collagen-induced arthritis (CIA) by normalizing the activated mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways ( 66 ). More biological studies are warranted to determine the relationship between RA and reduction in dementia.…”

Section: Discussionmentioning

confidence: 99%

Association between systemic rheumatic diseases and dementia risk: A meta-analysis

Wang

Lin²,

Huang³

et al. 2022

Front. Immunol.

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Background and aimsEpidemiological studies have been conducted on the relationship between systemic rheumatic diseases (SRDs) and dementia. Therefore, we focused on determining the extent of alliances bounded by SRDs, along with the risk of dementia.Materials and methodsTwo independent reviewers assessed all studies retrieved from the PubMed, EMBASE, Scopus, and Web of Science databases between January 1, 2000 and November 30, 2021. Only observational studies that estimated the possibility of dementia in participants with SRD were considered. The random-effects model was applied to forecast pooled risk ratios (RRs) and 95% confidence intervals (CI). Heterogeneity among the studies was evaluated using the Q and I2 statistics. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Funnel plots were used to calculate the risk of bias.ResultsSeventeen observational studies with 17,717,473 participants were recruited. Our findings showed that among the participants with SRDs, those with osteoarthritis, systemic lupus erythematosus, and Sjogren’s syndrome were highly related to an elevated risk of dementia (pooled RR: 1.31; 95% CI: 1.15–1.49, p<0.001; pooled RR: 1.43; 95% CI: 1.19–1.73, p<0.001; and pooled RR: 1.26; 95% CI: 1.14–1.39, p<0.001, respectively). However, participants with rheumatoid arthritis (RA) were not associated with an increased risk of dementia (pooled RR: 0.98; 95% CI: 0.90–1.07, p<0.001).ConclusionThis systematic review and meta-analysis demonstrated an increased dementia risk among SRDs participants, except for RA.

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“…[11][12][13][14]16 Interestingly, diclofenac appeared to regulate osteoclast differentiation by stabilizing the inactive form of NF-κB, 13 whereas ibuprofen given to rats with collagen-induced arthritis inhibited neuroinflammation in the hippocampus by attenuating the NF-κB cascade, and contributed to the memory improvement. 18 This latter example shows that the presence of inflammatory processes and activation of the immune system may affect the CNS and trigger or exacerbate neuroinflammation. It was further demonstrated that inflammatory mediators are implicated in depressive symptoms by directly affecting brain tissue, modulating the monoaminergic system and initiating neurotoxic processes in brain areas responsible for emotions and emotional memories.…”

Section: Nsaids Anti-inflammatory Mechanism Of Action Through the Nf-κbmentioning

confidence: 99%

PPARγ, NF-κB and the UPR pathway as new molecular targets in the anti-inflammatory actions of NSAIDs: Novel applications in cancers and central nervous system diseases?

Sokołowska,

Bleibel,

Owczarek

et al. 2024

Adv Clin Exp Med

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Ibuprofen treatment ameliorates memory deficits in rats with collagen-induced arthritis by normalizing aberrant MAPK/NF-κB and glutamatergic pathways

Cited by 5 publications

References 53 publications

Itaconate promotes hepatocellular carcinoma progression by epigenetic induction of CD8+ T-cell exhaustion

Itaconate promotes hepatocellular carcinoma progression by epigenetic induction of CD8+ T-cell exhaustion

Association between systemic rheumatic diseases and dementia risk: A meta-analysis

PPARγ, NF-κB and the UPR pathway as new molecular targets in the anti-inflammatory actions of NSAIDs: Novel applications in cancers and central nervous system diseases?

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