Transglutaminase 2 silencing reduced the beta-amyloid-effects on the activation of human THP-1 cells

Monica Currò, Nadia Ferlazzo, Salvatore Condello, Daniela Caccamo, Riccardo Ientile*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The aberrant expression and activation of transglutaminase 2 (TG2), the ubiquitous enzyme which catalyzes calcium-dependent protein cross-linking reactions, has been reported in many inflammatory diseases. Chronic inflammation, mediated by prolonged activation of brain-resident immunocompetent cells, appears to be involved in the pathogenesis of several age-related diseases, such as Alzheimer's disease. Given that increased TG2 expression has been observed in AD brains, this study was aimed to characterize the role of TG2 in THP-1 monocytes stimulated with amyloid-beta (Aβ). Aβ 1-42 treatment dose-dependently increased TG2 expression in THP-1 cells. In particular, a fivefold up-regulation of TG2, compared with control cells, was observed in the presence of 0.5 μM Aβ1-42. At the same concentration, Aβ1-42 was able to promote monocyte maturation as suggested by increased expression of the cell surface antigen CD14 as well as the adhesion-promoting factor fibronectin. The stimulation of THP-1 cells with Aβ1-42 also led to a significant up-regulation of tumor necrosis factor α (TNF-α) and matrix metalloproteinase 9 (MMP-9). Interestingly, THP-1 cell transfection with small interfering RNA directed against TG2 was able to reduce Aβ1-42 increased levels of all the examined markers of monocyte maturation (CD14, fibronectin), and activation (TNF-α, MMP-9). These results indicate that TG2 up-regulation is required for the functional THP-1 monocyte activation induced by Aβ1-42. This work suggests that TG2 inhibition may represent a therapeutic target to ameliorate the inflammation and progression in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)1427-1433
Number of pages7
JournalAmino Acids
Volume39
Issue number5
DOIs
StatePublished - Nov 1 2010

Keywords

  • Amyloid-beta
  • Inflammation
  • THP-1 monocyte activation
  • Transglutaminase 2
  • Transglutaminase 2 silencing

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Transglutaminase 2 silencing reduced the beta-amyloid-effects on the activation of human THP-1 cells'. Together they form a unique fingerprint.

Cite this