BACTERIAL PATHOGEN-ASSOCIATED MOLECULAR PATTERNS UPREGULATE HUMAN GLUCOCORTICOID RECEPTOR EXPRESSION IN PERIPHERAL...

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• Pathogen-associated molecular patterns (PAMPs) trigger pro-inflammatory responses via pattern recognition receptors.
• The mechanisms for downregulating inflammation initiated by bacterial components are not fully understood.

Purpose of the Study:

• To investigate whether bacterial products induce compensatory anti-inflammatory responses.
• To test the hypothesis that bacterial products induce the expression of the human glucocorticoid receptor (hGR).

Main Methods:

• Peripheral blood mononuclear cells (PBMCs) were isolated from human Leukopaks.
• PBMCs were treated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or peptidoglycan (PGN).
• hGR protein and mRNA expression were analyzed using Western blot and RT-PCR.

Main Results:

• LPS and PGN treatment increased hGRα protein expression in some PBMCs.
• PGN demonstrated a dose-dependent increase in hGRα expression.
• PGN also increased mRNA expression of an hGR splice variant, hGR-B(54).
• LTA did not affect hGRα expression.

Conclusions:

• Cell wall components from both gram-negative (LPS) and gram-positive (PGN) bacteria can upregulate hGRα expression.
• The same PAMPs that augment inflammation appear to initiate a negative feedback loop by inducing hGRα.
• This upregulation of hGRα may lead to the induction of anti-inflammatory proteins, helping to resolve inflammation.