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

Yudy Tjahjono, Caroline, Jusak Nugraha, Kuncoro Foe, Srikanth Karnati, Süleyman Ergün, Nico Jafet, Oryza Chrisantia, I. Made Andika Bara Kusuma, Hendy Wijaya, Wuryanto Hadinugroho, Dwi Aris Agung Nugrahaningsih, Dwi Liliek Kusindarta, Yufita Ratnasari Wilianto, Senny Yesery Esar, Hevi Wihadmadyatami

Research output: Contribution to journalArticlepeer-review

Abstract

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-CH2Cl), has been reported to have less gastric mucosal damage. However, the effect of 3-CH2Cl on CD4+ Tregs in LPS-induced mice is still unknown. Therefore, the present study was conducted to investigate the immunomodulatory effect of 3-CH2Cl on CD4+ T-cell and CD4+ Treg populations as well as FoxP3 expression in LPS-induced mice. METHODS: Synthesis of 3-CH2Cl was performed by mixing salicylic acid and chloromethylbenzoylchloride with the catalyzation of pyridine, acetone and heat. The 3-CH2Cl 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-CH2Cl 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-CH2Cl or ASA were higher than those treated with LPS merely. CONCLUSION: Since 3-CH2Cl 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.

Original languageEnglish
Pages (from-to)339-346
Number of pages8
JournalIndonesian Biomedical Journal
Volume15
Issue number4
DOIs
Publication statusPublished - 2023

Keywords

  • 2-(3-(chloromethyl)benzoyloxy)benzoic acid
  • CD4
  • FoxP3
  • LPS
  • T-regulatory cells
  • acetylsalicylic acid

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