TNF-α induces expression of the circadian clock gene Bmal1 via dual calcium-dependent pathways in rheumatoid synovial cells

Yoshida, Kohsuke; Nakai, Ayako; Kaneshiro, Kenta; Hashimoto, Naonori; Suzuki, Kazuhisa; Uchida, Koto; Hashimoto, Teppei; Kawasaki, Yoshiaki; Tateishi, Kensuke; Nakagawa, Natsuko; Shibanuma, Nao; Sakai, Yoshitada; Hashiramoto, Akira

doi:10.1016/j.bbrc.2017.12.015

Cited by 35 publications

(23 citation statements)

References 20 publications

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“…In keeping with in vitro studies, Rev-erbα expression was highly sensitive to inflammation 34 . Earlier work has identified changes in the expression of components of the core clock within synovial fibroblasts in the setting of chronic arthritis [35][36][37][38] , but this is to our knowledge the first observation of the effects of chronic joint inflammation on the intrinsic clock within macrophages and neutrophils. Whether the amplitude of residual intrinsic oscillations in pro-inflammatory cells is sufficient to maintain circadian control of immune activities remains to be determined.…”

Section: Discussionmentioning

confidence: 73%

Regulatory T cells confer a circadian signature on inflammatory arthritis

et al. 2020

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The circadian clock is an intrinsic oscillator that imparts 24 h rhythms on immunity. This clock drives rhythmic repression of inflammatory arthritis during the night in mice, but mechanisms underlying this effect are not clear. Here we show that the amplitude of intrinsic oscillators within macrophages and neutrophils is limited by the chronic inflammatory environment, suggesting that rhythms in inflammatory mediators might not be a direct consequence of intrinsic clocks. Anti-inflammatory regulatory T (Treg) cells within the joints show diurnal variation, with numbers peaking during the nadir of inflammation. Furthermore, the anti-inflammatory action of Treg cells on innate immune cells contributes to the nighttime repression of inflammation. Treg cells do not seem to have intrinsic circadian oscillators, suggesting that rhythmic function might be a consequence of external signals. These data support a model in which non-rhythmic Treg cells are driven to rhythmic activity by systemic signals to confer a circadian signature to chronic arthritis.

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Section: Discussionmentioning

confidence: 73%

Regulatory T cells confer a circadian signature on inflammatory arthritis

et al. 2020

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“… 15 Inhibiting the expression of TNF-α could significantly reduce the incidence of RA. 16 – 17 In this work, results showed that PF at the doses of 1.625 to 26 μg·mL −1 can reduce the inhibitory effect of TNF-α on L929 cell growth in a dose-dependent manner ( Figure 2 ). Morphological observations showed that the cells treated by PF were significantly improved, whereas TNF-α-treated cells showed a decrease in cell density, morphological changes, refractive degeneration, and the proliferation of crinkled cells ( Figure 3 ).…”

Section: Discussionmentioning

confidence: 56%

Paeoniflorin Antagonizes TNF-α-Induced L929 Fibroblastoma Cells Apoptosis by Inhibiting NF-κBp65 Activation

2018

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Paeoniflorin (PF) is one of the main pharmacodynamic components of Paeonia suffruticosa Andr, which has a significant anti-inflammatory effect on rheumatoid arthritis (RA), with a mechanism related to the tumor necrosis factor α (TNF-α). The aim of the present study was to investigate the role of PF in the apoptosis and expression of NF-κBp65 of L929 fibroblastoma cells induced by TNF-α. Our results showed that different concentrations of PF can significantly reduce the growth inhibition of L929 cells. Moreover, morphological observations, Hoechst 33342 staining, and flow cytometry detection of apoptosis showed that PF can significantly attenuate the TNF-α-induced apoptosis in a dose-dependent manner. Western blot analysis revealed that TNF-α induced the activation of NF-κBp65, whereas PF treatment had a marked dose-dependent suppression on it, which indicates that its action might be associated with inhibiting NF-κB signaling pathway. These results show that PF exerts a beneficial effect on L929 cells to prevent TNF-α-induced apoptosis and expression of NF-κBp65, which would be helpful to clarify its role in the treatment of RA.

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“…The effect of TNF on Per1 gene expression was dependent on p38, mitogen-activated protein kinase, and/or calcium signaling [22]. On the contrary, TNF enhanced the expression of BMAL1 and did not affect, or slightly enhanced, the expression of PER1 in human monocytic THP-1 cells [16, 42-44]. In addition, previous studies have also reported an association between TNFRp55 and clock genes.…”

Section: Discussionmentioning

confidence: 97%

Peripheral Neuroimmunoendocrine Interactions: Contribution of TNFRp55 to the Circadian Synchronization of Progesterone and Cytokine Production in Joints of Mice in Late Pregnancy

Arias

Mayordomo

Silva

et al. 2018

Neuroimmunomodulation

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Objective: Circadian rhythms are generated by the suprachiasmatic nucleus of the hypothalamus and involve rhythmic expression of clock genes and proteins. This rhythmicity is transferred to peripheral tissues by neural and hormonal signals. Late pregnancy is considered a state of inflammation which impacts on peripheral tissues such as joints. Tumor necrosis factor (TNF) mediates inflammatory and circadian responses through its p55 receptor (TNFRp55). Neuroimmunoendocrine interactions in joints have not been studied completely. The purpose of this study was to analyze these interactions, investigating the circadian rhythms of progesterone (Pg) and pro- and anti-inflammatory cytokines in the joints at the end of pregnancy (gestational day 18). Moreover, the impact of TNFRp55 deficiency on these temporal oscillations was explored. Methods: Wild-type and TNFRp55-deficient (KO) C57BL/6 mice were kept under constant darkness in order to study their endogenous circadian rhythms. The expression of the clock genes Bmal1 and Per1 at circadian time 7 was studied by reverse transcription polymerase chain reaction in the ankle joints of nonpregnant and pregnant (gestational day 18) mice. In late pregnancy, Pg and the cytokines interleukin 17 (IL-17), IL-6, and IL-10 were measured in the joints throughout a 24-h period by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Results: A significant increase in Bmal1 and Per1 mRNA expression was detected in the joints of pregnant KO mice. Furthermore, KO mice displayed a desynchronization of articular Pg and cytokine production. Conclusions: Our results show that TNF, via TNFRp55 signaling, modulates articular Pg and cytokine circadian rhythms in late pregnancy. These findings suggest a temporal neuroimmunoendocrine association in peripheral tissues in late pregnancy.

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TNF-α induces expression of the circadian clock gene Bmal1 via dual calcium-dependent pathways in rheumatoid synovial cells

Cited by 35 publications

References 20 publications

Regulatory T cells confer a circadian signature on inflammatory arthritis

Regulatory T cells confer a circadian signature on inflammatory arthritis

Paeoniflorin Antagonizes TNF-α-Induced L929 Fibroblastoma Cells Apoptosis by Inhibiting NF-κBp65 Activation

Peripheral Neuroimmunoendocrine Interactions: Contribution of TNFRp55 to the Circadian Synchronization of Progesterone and Cytokine Production in Joints of Mice in Late Pregnancy

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