Jurkat cell proliferation is suppressed by Chlamydia (Chlamydophila) pneumoniae infection accompanied with attenuation of phosphorylation at Thr389 of host cellular p70S6K

Hirai, Itaru; Ebara, Megumi; Nakanishi, Shoko; Yamamoto, Chiyo; Sasaki, Tadahiro; Ikuta, Kazuyoshi; Yamamoto, Yoshimasa

doi:10.1016/j.imbio.2012.06.008

Cited by 4 publications

(3 citation statements)

References 47 publications

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“…Due to the early alteration in RPS6 activity in response to the exposure to these two compounds, it can be expected these two compounds also target a protein/kinase located in the mTORC1-p70S6K pathway. Similar results have been reported; Chlamydia (Chlamydophila) pneumoniae infection activated Akt at both the Thr308 and Ser473 positions in Jurkat cells, whereas p70S6K phosphorylation was inhibited (Hirai et al, 2013).…”

Section: Discussionsupporting

confidence: 88%

Protein phosphorylation profiling identifies potential mechanisms for direct immunotoxicity

Shao

Stout

Hendriksen

et al. 2015

Journal of Immunotoxicology

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Signaling networks are essential elements that are involved in diverse cellular processes. One group of fundamental components in various signaling pathways concerns protein tyrosine kinases (PTK). Various toxicants have been demonstrated to exert their toxicity via modulation of tyrosine kinase activity. The present study aimed to identify common cellular signaling pathways that are involved in chemical-induced direct immunotoxicity. To this end, an antibody array-based profiling approach was applied to assess effects of five immunotoxicants, two immunosuppressive drugs and two non-immunotoxic control chemicals on the phosphorylation of 28 receptor tyrosine kinases and 11 crucial signaling nodes in Jurkat T-cells. The phosphorylation of ribosomal protein S6 (RPS6) and of kinases Akt, Src and p44/42 were found to be commonly regulated by immunotoxicants and/or immunosuppressive drugs (at least three compounds), with the largest effect observed upon RPS6. Flow cytometry and Western blotting were used to further examine the effect of the model immunotoxicant TBTO on the components of the mTOR-p70S6K-RPS6 pathway. These analyses revealed that both TBTO and the mTOR inhibitor rapamycin inactivate RPS6, but via different mechanisms. Finally, a comparison of the protein phosphorylation data to previously obtained transcriptome data of TBTO-treated Jurkat cells resulted in a good correlation at the pathway level and indicated that TBTO affects ribosome biogenesis and leukocyte migration. The effect of TBTO on the latter process was confirmed using a CXCL12 chemotaxis assay.

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Section: Discussionsupporting

confidence: 88%

Protein phosphorylation profiling identifies potential mechanisms for direct immunotoxicity

Shao

Stout

Hendriksen

et al. 2015

Journal of Immunotoxicology

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“…Coombes and Mohony (36) found that Akt phosphorylation at Ser 473 was also detected for the duration of the experiment (2 h) after the addition of C. pneumoniae to the cells. Recently, C. pneumoniae infection has been shown to induce Akt phosphorylations at Thr 308 and Ser 473 (45). These studies suggest that C. pneumoniae infection can increase the level of phosphorylated Akt, partially supporting our findings.…”

Section: Figsupporting

confidence: 91%

Chlamydia pneumoniae Infection Promotes Vascular Smooth Muscle Cell Migration through a Toll-Like Receptor 2-Related Signaling Pathway

Wang

Zhang

et al. 2013

Infect Immun

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The migration of vascular smooth muscle cells (VSMCs) from the media to the intima is proposed to be a key event in the development of atherosclerosis. Recently, we reported that Chlamydia pneumoniae infection is involved in VSMC migration. However, the exact mechanisms for C. pneumoniae infection-induced VSMC migration are not yet well elucidated. In this study, we examined the role of the Toll-like receptor 2 (TLR2) activation-related signaling pathway in VSMC migration induced by C. pneumoniae infection. An Affymetrix-based gene expression array was conducted to identify the changes of gene expression in rat primary VSMCs (rVSMCs) infected with C. pneumoniae. Both the microarray analysis and quantitative real-time reverse transcription (RT)-PCR revealed that TLR2 mRNA expression was strongly upregulated 12 h after C. pneumoniae infection. RT-PCR and Western blot analysis further showed that the expression levels of TLR2 mRNA and protein significantly increased at the different time points after infection. Immunocytochemical analysis suggested a TLR2 recruitment to the vicinity of C. pneumoniae inclusions. Cell migration assays showed that the TLR2-neutralizing antibody could significantly inhibit C. pneumoniae infection-induced rVSMC migration. In addition, C. pneumoniae infection stimulated Akt phosphorylation at Ser 473, which was obviously suppressed by the PI3K inhibitor LY294002, thereby inhibiting rVSMC migration caused by C. pneumoniae infection. Furthermore, both the infection-induced Akt phosphorylation and rVSMC migration were suppressed by the TLR2-neutralizing antibody. Taken together, these data suggest that C. pneumoniae infection can promote VSMC migration possibly through the TLR2-related signaling pathway.

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“…Due to the early alteration in RPS6 activity in response to the exposure to these two compounds, it can be expected that these two compounds also target a protein/kinase located in the mTORC1-p70S6K pathway. Similar results have been reported before, as Chlamydia (Chlamydophila) pneumoniae infection activated Akt at both Thr308 and Ser473 positions in Jurkat cells, whereas the phosphorylation of p70S6K was inhibited (Hirai et al, 2013).…”

supporting

confidence: 89%

Application of omics to immunotoxicology : from mechanisms of action to alternative testing strategies

Shao¹

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show abstract

Jurkat cell proliferation is suppressed by Chlamydia (Chlamydophila) pneumoniae infection accompanied with attenuation of phosphorylation at Thr389 of host cellular p70S6K

Cited by 4 publications

References 47 publications

Protein phosphorylation profiling identifies potential mechanisms for direct immunotoxicity

Protein phosphorylation profiling identifies potential mechanisms for direct immunotoxicity

Chlamydia pneumoniae Infection Promotes Vascular Smooth Muscle Cell Migration through a Toll-Like Receptor 2-Related Signaling Pathway

Application of omics to immunotoxicology : from mechanisms of action to alternative testing strategies

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