The Indonesian Biomedical Journal
Vol 15, No 4 (2023)

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

Yudy Tjahjono (Faculty of Pharmacy, Universitas Katolik Widya Mandala Surabaya, Jl. Kalisari Selatan 1, Surabaya 60237)
Caroline Caroline (Faculty of Pharmacy, Universitas Katolik Widya Mandala Surabaya, Jl. Kalisari Selatan 1, Surabaya 60237)
Jusak Nugraha (Department of Clinical Pathology, Faculty of Medicine, Universitas Airlangga, Jl. Mayjen Prof. Dr. Moestopo No.47, Surabaya 60132)
Kuncoro Foe (Faculty of Pharmacy, Universitas Katolik Widya Mandala Surabaya, Jl. Kalisari Selatan 1, Surabaya 60237)
Srikanth Karnati (Institute of Anatomy and Cell Biology, Julius-Maximilians-University Würzburg, Koellikerstraße 6, Würzburg 97070)
Süleyman Ergün (Institute of Anatomy and Cell Biology, Julius-Maximilians-University Würzburg, Koellikerstraße 6, Würzburg 97070)
Nico Jafet (Faculty of Pharmacy, Universitas Katolik Widya Mandala Surabaya, Jl. Kalisari Selatan 1, Surabaya 60237)
Oryza Chrisantia (Faculty of Pharmacy, Universitas Katolik Widya Mandala Surabaya, Jl. Kalisari Selatan 1, Surabaya 60237)
I Made Andika Bara Kusuma (Faculty of Pharmacy, Universitas Katolik Widya Mandala Surabaya, Jl. Kalisari Selatan 1, Surabaya 60237)
Hendy Wijaya (Faculty of Pharmacy, Universitas Katolik Widya Mandala Surabaya, Jl. Kalisari Selatan 1, Surabaya 60237)
Wuryanto Hadinugroho (Faculty of Pharmacy, Universitas Katolik Widya Mandala Surabaya, Jl. Kalisari Selatan 1, Surabaya 60237)
Dwi Aris Agung Nugrahaningsih (Department of Pharmacology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Jl. Farmako Sekip Utara, Yogyakarta 55281)
Dwi Liliek Kusindarta (Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Jl. Fauna No.2 Karangmalang, Yogyakarta 55281)
Yufita Ratnasari Wilianto (Faculty of Pharmacy, Universitas Katolik Widya Mandala Surabaya, Jl. Kalisari Selatan 1, Surabaya 60237)
Senny Yesery Esar (Faculty of Pharmacy, Universitas Katolik Widya Mandala Surabaya, Jl. Kalisari Selatan 1, Surabaya 60237)
Hevi Wihadmadyatami (Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Jl. Fauna No.2 Karangmalang, Yogyakarta 55281)



Article Info

Publish Date
25 Aug 2023

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 LPS-induced inflammation, it may act as a potential therapeutic drug to reduce inflammatory conditions.KEYWORDS: 2-(3-(chloromethyl)benzoyloxy)benzoic acid, acetylsalicylic acid, CD4, T-regulatory cells, FoxP3, LPS

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