Inhibition of FKBP5 Alleviates Inflammation and Intestinal Barrier Dysfunction in Sepsis

Area of Science:

• Gastroenterology
• Immunology
• Molecular Biology

Background:

• FK506 binding protein 5 (FKBP5) is known for its roles in acute kidney injury during sepsis.
• The specific functions and mechanisms of FKBP5 in sepsis-related intestinal injury are not well understood.
• This study investigates FKBP5's impact on intestinal injury in sepsis models.

Purpose of the Study:

• To elucidate the role of FKBP5 in sepsis-induced intestinal injury.
• To examine the effects of FKBP5 knockdown on intestinal barrier function, inflammation, and apoptosis.
• To investigate the involvement of nuclear factor kappa B (NF-κB) signaling in FKBP5-mediated effects.

Main Methods:

• Established mouse sepsis model using cecal ligation and puncture (CLP).
• Utilized a Caco-2 cell model stimulated with lipopolysaccharide (LPS).
• Assessed FKBP5 knockdown effects on apoptosis, barrier integrity markers (zonula occludens-1, occludin), inflammatory cytokines (TNF-α, IL-6, IL-1β), and NF-κB signaling.

Main Results:

• FKBP5 expression increased in ileal tissue and Caco-2 cells following CLP and LPS treatment, respectively.
• FKBP5 knockdown reduced apoptosis, improved intestinal barrier function, and decreased inflammatory markers in sepsis models.
• FKBP5 knockdown inhibited NF-κB signaling activation in both in vivo and in vitro sepsis models.

Conclusions:

• FKBP5 plays a significant role in promoting inflammation and intestinal barrier dysfunction during sepsis.
• Inhibiting FKBP5 demonstrates protective effects against sepsis-induced intestinal injury.
• Suppression of NF-κB signaling is a key mechanism through which FKBP5 inhibition exerts its protective effects.