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Dipyrone & 2,5-dimethylcelecoxib suppress Th2-related chemokine production in monocyte
Jeng-Chuan Shiang1, Ren-Long Jan2, Ming-Kai Tsai1, Chong-Chao Hsieh3, Hsuan-Fu Kuo4, Chang-Hung Kuo5, San-Nan Yang6, Ming-Yii Huang7, Li-Chen Chen8, Chih-Hsing Hung9
1 Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
2 Department of Pediatrics, Chi Mei Medical Center, Liouying, Taiwan
3 Division of Cardiac Surgery, Department of Surgery, Kaohsiung Medical University; Kaohsiung, Taiwan
4 Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University; Kaohsiung, Taiwan
5 Graduate Institute of Medicine, Kaohsiung Medical University Hospital; Department of Pediatrics, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
6 Graduate Institute of Medicine, Kaohsiung Medical University Hospital; Department of Pediatrics, Faculty of Medicine; Department of Pediatrics, Faculty of Pediatrics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
7 Department of Radiation Oncology, Kaohsiung Medical University Hospital; Department of Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
8 Kaohsiung Medical University Hospital, Taiwan
9 Graduate Institute of Medicine, Kaohsiung Medical University Hospital; Department of Pediatrics, Faculty of Medicine; Department of Pediatrics, Faculty of Pediatrics, College of Medicine, Kaohsiung Medical University; Department of Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
Correspondence Address:
Chih-Hsing Hung
Department of Pediatrics, Kaohsiung Medical University Hospital Kaohsiung Medical University, No.100, Tz-You 1st Road, Kaohsiung 807
Taiwan
 Source of Support: None, Conflict of Interest: None  | Check |
PMID: 25222785 
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Background & objectives: Selective cyclooxygenase-2 (COX-2) inhibitor is a form of thnon steroidal anti-inflammatory drug (NSAID) and is commonly used in autoimmune and rheumatic diseases to control inflammation and alleviate pain. Tumour necrosis factor-alpha (TNF-α) production and an imbalance of T helper 1 (Th1)/Th2 contribute to the pathogenesis of autoimmune and also anti-tumour activity. Dipyrone is a NSAID used to treat pain worldwide. The celecoxib analogue, 2,5-dimethylcelecoxib (DMC), lacks COX-2 inhibitory activity but exhibits anti-tumour properties. However, the effects and the mechanisms of dipyrone and 2,5-dimethylcelecoxib on tumour necrosis factor (TNF)-α and Th1- and Th2-related chemokines in monocytes remain poorly defined. This study was carried out to investigate the effects of dipyrone and 2,5-dimethylcelecoxib on the expression of Th1 (IP-10) and Th2 (I-309 and MDC) and TNF-α in human monocytes and the associated intracellular mechanism.
Methods: THP-1 cells and peripheral blood mononuclear cells (PBMCs) were pre-treated with dipyrone (10 -9 - 10 -4 M) and 2,5-dimethylcelecoxib (10 -9 - 10 -5 M) 2 h before lipopolysaccharide (LPS) stimulation. Cell supernatant was collected 24 h after LPS stimulation. TNF-α, I-309, MDC and IP-10 concentrations of cell supernatants were determined using ELISA. Intracellular signaling was evaluated by w0 estern blot.
Results: Dipyrone and 2,5-dimethylcelecoxib downregulated LPS-induced Th2-related chemokine I-309 and macrophage derived chemokine (MDC) production. Only high dose of 2,5-dimethylcelecoxib (10 -5 M), but not dipyrone downregulated LPS-induced IP-10. Only very high dose of 2,5-dimethylcelecoxib had effect on LPS-induced TNF-α expression in PBMCs. Dipyrone and 2,5-dimethylcelecoxib suppressed LPS-induced p65 and JNK MAPK (C-Jun N-terminal kinase mitogen activated protein kinase). expression.
Interpretation & conclusions: Dipyrone and 2,5-dimethylcelecoxib downregulated LPS-induced Th2-related chemokine I-309 and MDC in THP-1 cells. The suppressive effect on Th2-related chemokine I-309 and MDC may involve the downregulation of LPS-induced JNK and p65 expression. |
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