Folic Acid Is Able to Polarize the Inflammatory Response in LPS Activated Microglia by Regulating Multiple Signaling Pathways.

Antonia Cianciulli,Rosaria Salvatore,Teresa Trotta,Chiara Porro,Maria Antonietta Panaro

doi:10.1155/2016/5240127

Antonia Cianciulli, Rosaria Salvatore + Show 3 more

Open Access

https://doi.org/10.1155/2016/5240127

Copy DOI

Abstract

We investigated the ability of folic acid to modulate the inflammatory responses of LPS activated BV-2 microglia cells and the signal transduction pathways involved. To this aim, the BV-2 cell line was exposed to LPS as a proinflammatory response inducer, in presence or absence of various concentrations of folic acid. The production of nitric oxide (NO) was determined by the Griess test. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-10 were determined by ELISA. Inducible NO synthase (iNOS), nuclear transcription factor-kappa B (NF-κB) p65, MAPKs protein, and suppressors of cytokine signaling (SOCS)1 and SOCS3 were analyzed by western blotting. TNF-α and IL-1β, as well as iNOS dependent NO production, resulted significantly inhibited by folic acid pretreatment in LPS-activated BV-2 cells. We also observed that folic acid dose-dependently upregulated both SOCS1 and SOCS3 expression in BV-2 cells, leading to an increased expression of the anti-inflammatory cytokine IL-10. Finally, p-IκBα, which indirectly reflects NF-κB complex activation, and JNK phosphorylation resulted dose-dependently downregulated by folic acid pretreatment of LPS-activated cells, whereas p38 MAPK phosphorylation resulted significantly upregulated by folic acid treatment. Overall, these results demonstrated that folic acid was able to modulate the inflammatory response in microglia cells, shifting proinflammatory versus anti-inflammatory responses through regulating multiple signaling pathways.

Highlights

Folic acid belongs to the vitamin B complex
P-IκBα, which indirectly reflects NF-κB complex activation, and JNK phosphorylation resulted dose-dependently downregulated by folic acid pretreatment of LPS-activated cells, whereas p38 MAPK phosphorylation resulted significantly upregulated by folic acid treatment
None of the 5– 50 μg/mL range concentrations of folic acid tested affected the viability of BV-2 microglial cells, folate 70 μg/mL resulted to be cytotoxic (Table 2)

Summary

Introduction

Folic acid belongs to the vitamin B complex. It is vital for red blood cells and for many other cells in the body. The form of folic acid occurring naturally in food is called “folate” and it is a water-soluble vitamin [1]. Previous studies have described anti-inflammatory effects exerted by folic acid, the mechanisms underlying these actions are still not yet fully clarified [2, 3]. It was reported that combined supplementation of micronutrients, folate, and vitamin B12 has a beneficial effect in reducing inflammation in pregnancy, acting on the levels of inflammatory cytokines [4]. Folate and vitamin B supplementation has been assessed as a potential clinical intervention in vascular disease [5, 6]. Kolb and Petrie reported that folate deficiency enhances the proinflammatory cytokine output of RAW264.7 monocytes, suggesting that a folate deficiency may exacerbate cardiovascular disease by augmenting proinflammatory signals in the monocytemacrophage lineage [8]

Methods

Results

Conclusion