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Inflammation

, Volume 40, Issue 5, pp 1606–1621 | Cite as

Thrombospondin-1 Production Regulates the Inflammatory Cytokine Secretion in THP-1 Cells Through NF-κB Signaling Pathway

  • Tian Xing
  • Yao Wang
  • Wen-jie Ding
  • Yuan-ling Li
  • Xiao-dong Hu
  • Cong Wang
  • Ao Ding
  • Ji-long Shen
ORIGINAL ARTICLE
  • 369 Downloads

Abstract

Thrombospondin-1 (TSP-1) is upregulated in several inflammatory diseases. Recent data have shown that macrophages from TSP-1-deficient mice have a reduced inflammatory phenotype, suggesting that TSP-1 plays a part in macrophage activation. DNA microarray approach revealed that Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) may induce the enhanced TSP-1 expression in human monocytes, suggesting a role of TSP-1-mediated pathogenesis in periodontitis. Until recently, the function of TSP-1 has been a matter of debate. In this study, we explored the role of TSP-1 in inflammatory cytokine secretions and its putative mechanism in pathogenesis of periodontitis. We demonstrated that TSP-1 expression was significantly upregulated in gingival tissues with periodontitis and in P. gingivalis LPS-stimulated THP-1 cells. Deficiency of TSP-1 by transfecting siRNAs decreased IL-6, IL-1β, and TNF-α secretions in THP-1 cells, whereas overexpression of TSP-1 resulted in an upregulation of IL-6, IL-1β, and TNF-α productions. Additional experiments showed that Pyrrolidine dithiocarbamate (PDTC) inhibited IL-6, IL-1β, and TNF-α expression induced by overexpression of TSP-1, accompanying with downregulation of phosphorylated p65 and IκBα protein levels in response to P. gingivalis LPS. These results indicated that TSP-1 played a significant role in P. gingivalis LPS-initiated inflammatory cytokines (IL-6, IL-1β, and TNF-α) secretions of THP-1 cells, and the NF-κB signaling is involved in its induction of expression. Thus, TSP-1 effectively elevated P. gingivalis LPS-induced inflammation mediated by the NF-κB pathway and may be critical for pathology of periodontitis.

KEY WORDS

TSP-1 P. gingivalis LPS IL-6 IL-1β TNF-α NF-κB signaling PDTC 

Notes

Acknowledgements

This study has been supported by the National Natural Science Foundation of China (81600845), the Provincial Natural Science Research Project of Colleges, and the Universities of Anhui Province (No. KJ2016A348).

Compliance with Ethical Standards

The study was approved by the Health Human Research Ethics Committee of Anhui Medical University.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Tian Xing
    • 1
    • 2
  • Yao Wang
    • 3
  • Wen-jie Ding
    • 3
  • Yuan-ling Li
    • 3
  • Xiao-dong Hu
    • 3
  • Cong Wang
    • 3
  • Ao Ding
    • 4
  • Ji-long Shen
    • 1
    • 3
  1. 1.Department of ImmunologyAnhui Medical UniversityHefeiChina
  2. 2.Key Laboratory of Oral Diseases Research of Anhui Province, Stomatologic Hospital and CollegeAnhui Medical UniversityHefeiChina
  3. 3.Department of Pathogen BiologyProvincial Laboratories of Pathogen Biology and ZoonosesHefeiChina
  4. 4.Stomatology Department of Affiliated Provincial HospitalAnhui Medical UniversityHefeiChina

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