The Effect of C-Phycocyanin on Microglia Activation Is Mediated by Toll-like Receptor 4.

Anna Piovan,Morena Zusso,Carla Argentini,Raffaella Filippini,Stefano Moro,Pietro Giusti

doi:10.3390/ijms23031440

Anna Piovan, Morena Zusso + Show 4 more

Open Access

https://doi.org/10.3390/ijms23031440

Copy DOI

Abstract

The blue-green alga Spirulina platensis is rich in phycocyanins, that exhibit a wide range of pharmacological actions. C-phycocyanin (C-PC), in particular, possesses hepatoprotective, nephroprotective, antioxidant, and anticancer effects. Furthermore, several studies have reported both anti- and proinflammatory properties of this pigment. However, the precise mechanism(s) of action of C-PC in these processes remain largely unknown. Therefore, here we explored the C-PC effect in in vitro microglia activation. The effect of C-PC on the expression and release of IL-1β and TNF-α and the activation of NF-κB was examined in primary microglia by real-time PCR, ELISA, and immunofluorescence. Treatment with C-PC up-regulated the expression and release of IL-1β and TNF-α. C-PC also promoted the nuclear translocation of the NF-κB transcription factor. Then, to elucidate the molecular mechanisms for the immunoregulatory function of C-PC, we focused on investigating the role of Toll-like receptor 4 (TLR4). Accordingly, several TLR4 inhibitors have been used. Curcumin, ciprofloxacin, L48H37, and CLI-095 that suppresses specifically TLR4 signaling, blocked IL-1β and TNF-α. Overall, these results indicate the immunomodulatory effect of C-PC in microglia cultures and show for the first time that the molecular mechanism implicated in this effect may involve TLR4 activation.

Highlights

The blue-green alga Arthrospira platensis, commonly known as Spirulina, has long been used as a food supplement mainly due to the high content of proteins (~70% by dry weight), vitamins, minerals, various kinds of amino acids, fibers, and pigments such as chlorophylls, carotenoids, and phycocyanins [1,2]
Chen et al [24] showed that C-PC induced secretion of tumor necrosis factor (TNF)-α, IL-1β, and IL-6, increased expression of COX-2, and stimulated the phosphorylation of proteins implicated in inflammatory responses, including ERK, JNK, p38 and IκB in murine macrophages
In an attempt to explain the inconsistency between our results and some previous studies that have shown the anti-inflammatory properties of C-PC in macrophage and microglia cultures [23,24], we examined whether C-PC could be contaminated with LPS

Summary

Introduction

The blue-green alga Arthrospira platensis, commonly known as Spirulina, has long been used as a food supplement mainly due to the high content of proteins (~70% by dry weight), vitamins, minerals, various kinds of amino acids, fibers, and pigments such as chlorophylls, carotenoids, and phycocyanins [1,2]. A lot of in vitro and in vivo studies have been focused on the antioxidant activity of Spirulina, that is able to activate antioxidant enzymes, scavenge free radicals and protect against lipid peroxidation and DNA damage [3,4,5,6]. Spirulina exhibits promising anti-inflammatory activities being able to inhibit the expression of inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β, and IL-6 in in vitro and in vivo models of inflammation [12,13,14]. Other studies reported neuroprotective effects of C-PC and showed that oral administration of C-PC crosses blood brain barrier suggesting its use in neurodegeneration, where oxidative stress and neuroinflammation play a relevant role [25,26]

Methods

Results

Conclusion