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Abstract: FR-PO1115

Alternative M2 Macrophages Activation and TGF-β1 Production Are Induced by TNF-α Through the Adenosine A2A Receptor Pathway

Session Information

  • Transplantation: Basic
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 1901 Transplantation: Basic

Authors

  • Diaz Encarnacion, Montserrat M., Fundación Puigvert, Barcelona, Spain
  • Guillen-gomez, Elena, Fundación Puigvert, Barcelona, Spain
  • Silva, Irene, Fundación Puigvert, Barcelona, Spain
  • Serra, Nuria, Fundación Puigvert, Barcelona, Spain
  • Ballarin, Jose, Fundación Puigvert, Barcelona, Spain
  • Caballero, Francisco, Hospital Santa Creu i Sant Pau, Barcelona, Spain
  • Guirado, Lluis, Fundación Puigvert, Barcelona, Spain
Background

Kidney transplants from deceased donors have a worse prognosis than those from living donors. Early and persistent inflammation may contribute to the development of fibrosis and impact transplant outcome. We showed previously that, in renal tissue from deceased donors, increased expression of A2A adenosine receptor, that could be involved in anti-inflammatory activity and M2 macrophage activation, correlated with inflammatory and anti-inflammatory mediators such as TNF-α and TGF-β1. The aim of this research is to study the association between TNF-α and A2A in macrophage phenotype differentiation.

Methods

THP-1 cells were seeded in the presence of TNF-α at different time-points (3, 6, 18 and 24 hours) and concentrations (5, 10 and 20 ng/ml). Cells were pretreated for 30 minutes with 1 µM of the A2AR antagonist ZM241385 before TNF-α was added and samples were analyzed by Real-time PCR.

Results

TNF-alpha significantly augmented the expression of A2A but not A2B at all points analyzed, reaching the maximum increase at a concentration of 10 ng/ml at 3 hours of treatment (p<0.001). TNF-α also induced the expression of TGF-β1 and the M2 marker CD163 at 18 and 24 hours (figure 1A). Interestingly, the expression the M1 macrophage marker CD86 decreased with TNF-α treatment. Pretreatment with ZM241385 abolished the effect of TNF-α over CD163 (figure 1B) and TGF-β1, providing evidence that A2A receptor is involved in M2 macrophage activation by TNF-α. In fact, induction of CD163 expression by IL-10 (p=0.0006) was partially but significantly blocked by ZM241385 (31.4% increase blocked, p=0.018). We did not detect any effect of IL-10 on TGF-β. The decrease in CD86 does not seem to involve the A2A purinergic pathway.

Conclusion

Our results suggest TNF-alpha induces macrophage M2 switching and TGF-β1 expression through A2a receptor activation.

Funding

  • Government Support - Non-U.S.