Tp47-Induced Monocyte-Derived Microvesicles Promote the Adherence of THP-1 Cells to Human Umbilical Vein Endothelial...

Area of Science:

• Immunology
• Cell Biology
• Vascular Biology

Background:

• Treponema pallidum protein Tp47 contributes to vascular inflammation by inducing immunocyte adherence.
• The role of microvesicles as inflammatory mediators between vascular and immunocytes is not fully understood.

Purpose of the Study:

• To investigate whether microvesicles derived from Tp47-treated cells (Tp47-microvesicles) mediate monocyte adhesion to endothelial cells.
• To elucidate the molecular mechanisms, including specific adhesion molecules and intracellular signaling pathways, involved in Tp47-microvesicle-induced inflammation.

Main Methods:

• Isolation of microvesicles from Tp47-treated THP-1 cells via differential centrifugation.
• Adherence assays using human umbilical vein endothelial cells (HUVECs) and THP-1 cells.
• Measurement of ICAM-1 and VCAM-1 expression in HUVECs.
• Investigation of intracellular signaling pathways (ERK1/2, NF-κB) using pathway inhibitors.

Main Results:

• Tp47-microvesicles significantly promoted THP-1 cell adhesion to HUVECs (P < 0.01).
• Tp47-microvesicles upregulated ICAM-1 and VCAM-1 expression in HUVECs (P < 0.001), and blocking these molecules inhibited adhesion.
• Activation of ERK1/2 and NF-κB pathways was observed in HUVECs treated with Tp47-microvesicles; inhibition of these pathways reduced adhesion molecule expression and monocyte adhesion.

Conclusions:

• Tp47-microvesicles act as functional inflammatory mediators, promoting monocyte adhesion to endothelial cells.
• The adhesion is mediated by upregulated ICAM-1 and VCAM-1 expression, driven by the activation of ERK1/2 and NF-κB signaling pathways.
• These findings offer insights into the vascular inflammatory processes in syphilis.