The Probiotic Mixture VSL#3 Alters the Morphology and Secretion Profile of Both Polarized and Unpolarized Human Macrophages in a Polarization-Dependent Manner
|Raymond A. Isidro1*, Fernando J. Bonilla1, Hendrick Pagan1, Myrella L. Cruz1, Pablo Lopez2, Lenin Godoy1, Siomara Hernández1, Raisa Y. Loucil-Alicea3, Vanessa Rivera-Amill2, Yasuhiro Yamamura2, Angel A. Isidro1,4 and Caroline B. Appleyard1|
|1Department of Physiology and Pharmacology, Ponce School of Medicine and Health Sciences, Ponce, PR 00716, USA|
|2Department of Microbiology, Ponce School of Medicine and Health Sciences, Ponce, PR 00716, USA|
|3Department of Biochemistry, Ponce School of Medicine and Health Sciences, Ponce, PR 00716, USA|
|4Department of Pathology, Ponce School of Medicine and Health Sciences, Ponce, PR 00716, USA|
|Corresponding Author :||Raymond A. Isidro, BS
Department of Physiology and Pharmacology
Ponce School of Medicine and Health Sciences
388 Zona Ind Reparada 2, Ponce, PR 00716-2347, USA
Tel: (787) 840-2575
Fax: (787) 841-1040
E-mail: [email protected]
|Received March 21, 2014; Accepted June 13, 2014; Published June 20, 2014|
|Citation: Isidro RA, Bonilla FJ, Pagan H, Cruz ML, Lopez P, et al. (2014) The Probiotic Mixture VSL#3 Alters the Morphology and Secretion Profile of Both Polarized and Unpolarized Human Macrophages in a Polarization-Dependent Manner. J Clin Cell Immunol 5:227. doi:10.4172/2155-9899.1000227|
|Copyright: © 2014 Isidro RA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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Background: Patients with Inflammatory Bowel Disease (IBD), most commonly Crohn’s disease (CD) or ulcerative colitis (UC), suffer from chronic intestinal inflammation of unknown etiology. Increased proinflammatory macrophages (M1) have been documented in tissue from patients with CD. Anti-inflammatory macrophages (M2) may play a role in UC given the preponderance of Th2 cytokines in this variant of IBD. Animal and clinical studies have shown that the probiotic VSL#3 can ameliorate signs and symptoms of IBD. Although animal data suggests a modulatory effect on macrophage phenotype, the effect of VSL#3 on human macrophages remains unknown.
Objective: To determine the effect of the probiotic VSL#3 on the phenotype of polarized (M1/M2) and unpolarized (MΦ) human macrophages.
Methods: Human monocyte-derived macrophages, generated by culturing monocytes with M-CSF, were left unpolarized or were polarized towards an M1 or an M2 phenotype by culture with LPS and IFN-γ or IL-4, respectively, and were then cultured in the presence or absence of VSL#3 for 3 days. Changes in macrophage morphology were assessed. Cytokine and chemokine levels in supernatants were determined by multiplex assay.
Results: VSL#3 decreased the granuloma-like aggregates of M1 macrophages, increased fibroblast-like M2 macrophages, and decreased fibroblast-like MΦ macrophages. VSL#3 increased the secretion of IL-1β, IL-6, IL-10, and G-CSF by M1, M2, and MΦ macrophages. VSL#3 exposure maintained the proinflammatory phenotype of M1 macrophages, sustaining IL-12 secretion, increasing IL-23 secretion, and decreasing MDC secretion. Both VSL#3- treated M2 and MΦ macrophages secreted higher levels of anti-inflammatory and pro-healing factors such as IL-1Ra, IL-13, EGF, FGF-2, TGF-α, and VEGF, as well as proinflammatory cytokines, including IL-12 and TNF-α.
Conclusion: Under our experimental conditions VSL#3 induced a mixed proinflammatory and anti-inflammatory phenotype in polarized and unpolarized macrophages. This differential effect could explain why patients with CD do not respond to probiotic therapy as well as patients with UC.