2-(3-(chloromethyl)benzoyloxy)benzoic Acid Increases CD4+ Regulatory T-Cell Population and FoxP3 Expression in Lipopolysaccharide-induced Mice

BACKGROUND: Lipopolysaccharide (LPS) has been reported to increase CD4+ regulatory T-cell (CD4+ Treg) populations. Acetylsalicylic acid (ASA) has been reported to have immunomodulatory activity, but it may induce chronic gastric ulceration. Another salicylic acid-bearing compound, 2-(3-(chloromethyl) benzoyloxy)benzoic acid (3-CH2 Cl), has been reported to have less gastric mucosal damage. However, the effect of 3-CH2 Cl on CD4+ Tregs in LPS-induced mice is still unknown. Therefore, the present study was conducted to
investigate the immunomodulatory effect of 3-CH2 Cl on CD4+
T-cell and CD4+ Treg populations as well as FoxP3
expression in LPS-induced mice.
METHODS: Synthesis of 3-CH2 Cl was performed by mixing salicylic acid and chloromethylbenzoylchloride with
the catalyzation of pyridine, acetone and heat. The 3-CH2
Cl tablets were prepared using direct compression method.
After intraperitoneal injection of 1 mg/kg BW LPS to mice,
60 mg/kg BW ASA or 60 mg/kg BW 3-CH2Cl was given orally for 3 days. The splenocyte was obtained through
splenectomy and collagenase digestion. The population
of CD4+ T-cells and CD4+ Tregs, as well as the splenic
FoxP3 expression were determined using flow cytometry
technique.
RESULTS: CD4+ T-cell populations in mice treated with
LPS and 3-CH2 Cl or ASA were lower than those treated with
LPS merely. Meanwhile, CD4+ Treg populations and FoxP3
expression levels in mice treated with LPS and 3-CH2
Cl or ASA were higher than those treated with LPS merely.
CONCLUSION: Since 3-CH2 Cl could decrease CD4+
T-cell population and increase CD4+ Treg population
mediated by the increase of FoxP3 expression in LPSinduced inflammation, it may act as a potential therapeutic
drug to reduce inflammatory conditions.