Evaluation of the Effect of Antidepressant Drug, Fluvoxamine, on Cyclooxygenase-2 Protein Expression in Lipopolysaccharide-stimulated Macrophages

Esfahani, Hajar Naji; Rafiee, Laleh; Haghjooy Javanmard, Shaghayegh

Evaluation of the Effect of Antidepressant Drug, Fluvoxamine, on Cyclooxygenase-2 Protein Expression in Lipopolysaccharide-stimulated Macrophages

Document Type : Original Article

Authors

Applied Physiology Research Center, Isfahan Cardiovascular Research Institute, Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Fluvoxamine, a well-known selective serotonin reuptake inhibitor, is used for the management of mental disorders and various types of chronic pain. In our previous study, we found the inhibitory effect of fluvoxamine on inflammatory mediator's expression. In the line of the indicated study, we sought to evaluate the effect of fluvoxamine on the expression of some inflammatory mediators such as cyclooxygenase-2 (COX-2). Materials and Methods: An in vitro model system of lipopolysaccharide-stimulated human U937 macrophages was used. The expression of COX-2 protein was measured by flow cytometry. Results: The expression of COX-2 significantly decreased by fluvoxamine in U937 macrophages. Conclusion: The results of the present study provide further evidence for the anti-inflammatory effect of fluvoxamine. This effect appears to be mediated by the downregulation of inflammatory genes. Further studies are needed to evaluate the complex cellular and molecular mechanisms of fluvoxamine.

Keywords

References

1.	Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010;67:446-57.
2.	Maes M, Song C, Lin AH, Bonaccorso S, Kenis G, De Jongh R, et al. Negative immunoregulatory effects of antidepressants: Inhibition of interferon-gamma and stimulation of interleukin-10 secretion. Neuropsychopharmacology 1999;20:370-9.
3.	Gobin V, Van Steendam K, Denys D, Deforce D. Selective serotonin reuptake inhibitors as a novel class of immunosuppressants. Int Immunopharmacol 2014;20:148-56.
4.	De Berardis D, Conti CM, Serroni N, Moschetta FS, Olivieri L, Carano A, et al. The effect of newer serotonin-noradrenalin antidepressants on cytokine production: A review of the current literature. Int J Immunopathol Pharmacol 2010;23:417-22.
5.	Hussein SZ, Mohd Yusoff K, Makpol S, Mohd Yusof YA. Gelam honey inhibits the production of proinflammatory, mediators NO, PGE (2), TNF-α, and IL-6 in carrageenan-induced acute paw edema in rats. Evid Based Complement Alternat Med 2012;2012:109636.
6.	McCoy JM, Wicks JR, Audoly LP. The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid arthritis. J Clin Invest 2002;110:651-8.
7.	Leonard BE. The immune system, depression and the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry 2001;25:767-80.
8.	Kuroda E, Yamashita U. Mechanisms of enhanced macrophage-mediated prostaglandin E2 production and its suppressive role in th1 activation in Th2-dominant BALB/c mice. J Immunol 2003;170:757-64.
9.	Sadeghi H, Hajhashemi V, Minaiyan M, Movahedian A, Talebi A. A study on the mechanisms involving the anti-inflammatory effect of amitriptyline in carrageenan-induced paw edema in rats. Eur J Pharmacol 2011;667:396-401.
10.	Fazzino F, Montes C, Urbina M, Carreira I, Lima L. Serotonin transporter is differentially localized in subpopulations of lymphocytes of major depression patients. Effect of fluoxetine on proliferation. J Neuroimmunol 2008;196:173-80.
11.	Faraj BA, Olkowski ZL, Jackson RT. Expression of a high-affinity serotonin transporter in human lymphocytes. Int J Immunopharmacol 1994;16:561-7.
12.	Urbina M, Pineda S, Piñango L, Carreira I, Lima L. [3H] Paroxetine binding to human peripheral lymphocyte membranes of patients with major depression before and after treatment with fluoxetine. Int J Immunopharmacol 1999;21:631-46.
13.	Tynan RJ, Weidenhofer J, Hinwood M, Cairns MJ, Day TA, Walker FR, et al. A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia. Brain Behav Immun 2012;26:469-79.
14.	Rafiee L, Hajhashemi V, Javanmard SH. Fluvoxamine inhibits some inflammatory genes expression in LPS/stimulated human endothelial cells, U937 macrophages, and carrageenan-induced paw edema in rat. Iran J Basic Med Sci 2016;19:977-84.
15.	DeWitt DL. Prostaglandin endoperoxide synthase: Regulation of enzyme expression. Biochim Biophys Acta 1991;1083:121-34.
16.	Taler M, Gil-Ad I, Lomnitski L, Korov I, Baharav E, Bar M, et al. Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression. Eur Neuropsychopharmacol 2007;17:774-80.
17.	Yaron I, Shirazi I, Judovich R, Levartovsky D, Caspi D, Yaron M, et al. Fluoxetine and amitriptyline inhibit nitric oxide, prostaglandin E2, and hyaluronic acid production in human synovial cells and synovial tissue cultures. Arthritis Rheum 1999;42:2561-8.
18.	Roumestan C, Michel A, Bichon F, Portet K, Detoc M, Henriquet C, et al. Anti-inflammatory properties of desipramine and fluoxetine. Respir Res 2007;8:35.
19.	Duman RS. Novel therapeutic approaches beyond the serotonin receptor. Biol Psychiatry 1998;44:324-35.
20.	Hashioka S, Klegeris A, Monji A, Kato T, Sawada M, McGeer PL, et al. Antidepressants inhibit interferon-gamma-induced microglial production of IL-6 and nitric oxide. Exp Neurol 2007;206:33-42.
21.	Delfino F, Walker WH. Hormonal regulation of the NF-kappaB signaling pathway. Mol Cell Endocrinol 1999;157:1-9.
22.	Ollivier V, Parry GC, Cobb RR, de Prost D, Mackman N. Elevated cyclic AMP inhibits NF-kappaB-mediated transcription in human monocytic cells and endothelial cells. J Biol Chem 1996;271:20828-35.
23.	Pober JS, Sessa WC. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 2007;7:803-15.
24.	Sharif O, Bolshakov VN, Raines S, Newham P, Perkins ND. Transcriptional profiling of the LPS induced NF-kappaB response in macrophages. BMC Immunol 2007;8:1.

Advanced Biomedical Research