LPS Induces mTORC1 and mTORC2 Activation During Monocyte Adhesion

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Monocyte adhesion is vital for immune cell transmigration.
• Lipopolysaccharide (LPS) is a known inducer of monocyte adhesion.
• The roles of mammalian target of rapamycin (mTOR) complexes and protein kinase C (PKC) in this process require further elucidation.

Purpose of the Study:

• To investigate the involvement of mTOR complexes (mTORC1 and mTORC2) and PKC in LPS-induced monocyte adhesion.
• To identify the molecular signaling pathways mediating monocyte adhesion.

Main Methods:

• Utilized THP-1 cells, a human monocytic cell line.
• Applied static and flow conditions to study monocyte adhesion.
• Employed inhibitors for mTOR (WYE-354, rapamycin), PI3K (wortmannin), MEK/ERK (U0126), and PKC (calphostin C).
• Assessed CD11a expression and actin cytoskeleton rearrangement.

Main Results:

• LPS increased PI3K/mTORC2 pathway and PKC activity.
• Inhibitors of mTORC1/mTORC2 and PI3K blocked monocyte adhesion and CD11a expression.
• Rapamycin and WYE-354 inhibited LPS-induced adhesion and actin rearrangement, confirming mTORC1 involvement.
• PKC activation mimicked LPS effects, activating the MEK/ERK/TSC2/mTORC1/S6K pathway and promoting adhesion.

Conclusions:

• LPS induces monocyte adhesion via activation of mTOR complexes and PKC.
• The MEK/ERK/TSC2 axis acts as a mediator in this signaling cascade.
• This study reveals a novel molecular mechanism underlying monocyte adhesion in immune-based diseases.