Iris pigment epithelial cells express a functional lipopolysaccharide receptor complex

Area of Science:

• Ocular immunology
• Inflammation research

Background:

• Acute anterior uveitis (AAU) pathogenesis may involve ocular pigment epithelial cells.
• Lipopolysaccharide (LPS) activation of Toll-like receptors (TLRs) is a potential trigger for AAU.

Purpose of the Study:

• To determine the expression of LPS receptors in iris pigment epithelium (IPE).
• To investigate the role of IPE in ocular inflammation.

Main Methods:

• Investigated LPS receptor complex (TLR4, MD-2, CD14) expression in human IPE using RT-PCR, flow cytometry, Western blot, and immunohistochemistry.
• Measured cytokine secretion from LPS-treated IPE via multiplex bead array and ELISA.
• Assessed CD14's role using soluble CD14 and antibody neutralization; examined in vivo CD14 expression.

Main Results:

• IPE cells expressed TLR4, MD-2, and CD14 in vitro.
• LPS stimulation induced secretion of proinflammatory cytokines (IL-6, CXCL8, CXCL10, CCL2, CCL4, CCL5) from IPE.
• CXCL8 secretion was dependent on CD14 and TLR4; CD14 was detected in iris and aqueous humor.

Conclusions:

• IPE cells possess a functional LPS receptor complex.
• IPE can promote ocular inflammation via secretion of proinflammatory mediators.
• CD14 is a critical modulator of the LPS response in IPE.