Dataset Information

Suppression of wear-particle-induced pro-inflammatory cytokine and chemokine production in macrophages via NF-?B decoy oligodeoxynucleotide: a preliminary report.

ABSTRACT: Total joint replacement (TJR) is very cost-effective surgery for end-stage arthritis. One important goal is to decrease the revision rate, mainly because TJR has been extended to younger patients. Continuous production of ultra-high molecular weight polyethylene (UHMWPE) wear particles induces macrophage infiltration and chronic inflammation, which can lead to periprosthetic osteolysis. Targeting individual pro-inflammatory cytokines directly has not reversed the osteolytic process in clinical trials, owing to compensatory up-regulation of other pro-inflammatory factors. It is hypothesized that targeting the important transcription factor NF-?B could mitigate the inflammatory response to wear particles, potentially diminishing osteolysis. In the current study, NF-?B activity in mouse RAW 264.7 and human THP1 macrophage cell lines, as well as primary mouse and human macrophages, was suppressed via competitive binding with double strand decoy oligodeoxynucleotide (ODN) containing an NF-?B binding element. It was found that macrophage exposure to UHMWPE particles induced multiple pro-inflammatory cytokine and chemokine expression, including TNF-?, MCP1, MIP1? and others. Importantly, the decoy ODN significantly suppressed the induced cytokine and chemokine expression in both murine and human macrophages, and resulted in suppression of macrophage recruitment. The strategic use of decoy NF-?B ODN, delivered locally, could potentially diminish particle-induced periprosthetic osteolysis.

SUBMITTER: Lin TH

PROVIDER: S-EPMC4081023 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Suppression of wear-particle-induced pro-inflammatory cytokine and chemokine production in macrophages via NF-κB decoy oligodeoxynucleotide: a preliminary report.

Lin Tzu-Hua TH Yao Zhenyu Z Sato Taishi T Keeney Michael M Li Chenguang C Pajarinen Jukka J Yang Fan F Egashira Kensuke K Goodman Stuart B SB

Acta biomaterialia 20140509 8

Total joint replacement (TJR) is very cost-effective surgery for end-stage arthritis. One important goal is to decrease the revision rate, mainly because TJR has been extended to younger patients. Continuous production of ultra-high molecular weight polyethylene (UHMWPE) wear particles induces macrophage infiltration and chronic inflammation, which can lead to periprosthetic osteolysis. Targeting individual pro-inflammatory cytokines directly has not reversed the osteolytic process in clinical t ...[more]

PMID: 24814879

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Project description:Long non-coding RNAs (lncRNAs) are transcripts of more than 200 nucleotides that are not translated into functional proteins. Cellular lncRNAs have been shown to act as regulators by interacting with target nucleic acids or proteins and modulating their activities. We investigated the role of RNA1.2, which is one of four major lncRNAs expressed by human cytomegalovirus (HCMV), by comparing the properties of parental virus in vitro with those of deletion mutants lacking either most of the RNA1.2 gene or only the TATA element of the promoter. In comparison with parental virus, these mutants exhibited no growth defects and minimal differences in viral gene expression in human fibroblasts. In contrast, 76 cellular genes were consistently up- or down-regulated by the mutants at both the RNA and protein levels at 72 hours after infection. Differential expression of the gene most highly upregulated by the mutants (Tumor protein p63-regulated gene 1-like protein; TPRG1L) was confirmed at both levels by RT-PCR and immunoblotting. Consistent with the known ability of TPRG1L to upregulate IL-6 expression via NF-κB stimulation, RNA1.2 mutant-infected fibroblasts were observed to upregulate IL-6 in addition to TPRG1L. Comparable surface expression of TNF receptors and responsiveness to TNF-α in cells infected by the parental and mutant viruses indicated that activation of signaling by TNF-α is not involved in upregulation of IL-6 by the mutants. In contrast, inhibition of NF-κB activity and knockdown of TPRG1L expression reduced the extracellular release of IL-6 by RNA1.2 mutant-infected cells, thus demonstrating that upregulation of TPRG1L activates NF-κB. The levels of CCL2 and CXCL1 transcripts were also increased in RNA1.2 mutant-infected cells, further demonstrating the presence of active NF-κB signalling. These results suggest that RNA1.2 plays a role in manipulating intrinsic NF-B-dependent cytokine and chemokine release during HCMV infection , thereby impacting downstream immune responses.

Dataset Information

Suppression of wear-particle-induced pro-inflammatory cytokine and chemokine production in macrophages via NF-?B decoy oligodeoxynucleotide: a preliminary report.

Publications

Suppression of wear-particle-induced pro-inflammatory cytokine and chemokine production in macrophages via NF-κB decoy oligodeoxynucleotide: a preliminary report.

Similar Datasets

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