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
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. © 2023 The Prodia Education and Research Institute.
Faculty of Pharmacy, Universitas Katolik Widya Mandala Surabaya, Jl. Kalisari Selatan 1, Surabaya, 60237, Indonesia; Doctoral Program of Veterinary Science, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Jl. Fauna No.2 Karangmalang, Yogyakarta, 55281, Indonesia; Department of Clinical Pathology, Faculty of Medicine, Universitas Airlangga, Jl. Mayjen Prof. Dr. Moestopo No.47, Surabaya, 60132, Indonesia; Institute of Anatomy and Cell Biology, Julius-Maximilians-University Würzburg, Koellikerstraße 6, Würzburg, 97070, Germany; Department of Pharmacology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Jl. Farmako Sekip Utara, Yogyakarta, 55281, Indonesia; Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Jl. Fauna No.2 Karangmalang, Yogyakarta, 55281, Indonesia