Differential pro-inflammatory responses of astrocytes and microglia involve STAT3 activation in response to 1800 MHz radiofrequency fields.

Yonghui Lu,Yue He,Mindi He,Chunhai Chen,Shangcheng Xu,Zhou Zhou,Chuan Liu,Zhengping Yu,Yang Zhang,Lei Zhang,Huifeng Pi,Michelle L Block

doi:10.1371/journal.pone.0108318

Abstract

Microglia and astrocytes play important role in maintaining the homeostasis of central nervous system (CNS). Several CNS impacts have been postulated to be associated with radiofrequency (RF) electromagnetic fields exposure. Given the important role of inflammation in neural physiopathologic processes, we investigated the pro-inflammatory responses of microglia and astrocytes and the involved mechanism in response to RF fields. Microglial N9 and astroglial C8-D1A cells were exposed to 1800 MHz RF for different time with or without pretreatment with STAT3 inhibitor. Microglia and astrocytes were activated by RF exposure indicated by up-regulated CD11b and glial fibrillary acidic protein (GFAP). However, RF exposure induced differential pro-inflammatory responses in astrocytes and microglia, characterized by different expression and release profiles of IL-1β, TNF-α, IL-6, PGE2, nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Moreover, the RF exposure activated STAT3 in microglia but not in astrocytes. Furthermore, the STAT3 inhibitor Stattic ameliorated the RF-induced release of pro-inflammatory cytokines in microglia but not in astrocytes. Our results demonstrated that RF exposure differentially induced pro-inflammatory responses in microglia and astrocytes, which involved differential activation of STAT3 in microglia and astrocytes. Our data provide novel insights into the potential mechanisms of the reported CNS impacts associated with mobile phone use and present STAT3 as a promising target to protect humans against increasing RF exposure.

Highlights

The growing use of mobile phones worldwide has provoked public concern regarding the potential risks of radiofrequency (RF) electromagnetic fields to the central nervous system (CNS)
Flow cytometry results showed that CD11b expression on surface of N9 cells increased after exposure to RF for 12 and 24 h compared with sham control (Figure 1A-F)
Immunoreactivity of glial fibrillary acidic protein (GFAP) was enhanced by 24-h RF exposure in astrocytes (Figure 2A), and it was further verified by western blot, showing that GFAP expression increased after exposure to RF for 24 h (Figure 2B, C)

Summary

Introduction

The growing use of mobile phones worldwide has provoked public concern regarding the potential risks of radiofrequency (RF) electromagnetic fields to the central nervous system (CNS). Several studies have reported that exposure to RF fields could induce headache [1], neuron and glial cell death [2,3], disturbances in neurotransmitter release [4] and cognitive impairments [5], and increase blood-brain barrier permeability [6]. There are lots of positive reports, it is still controversial whether RF exposure leads to these CNS impacts. Some of these effects were not observed by some other studies after RF exposure [7,8,9,10]. Long-term exposure to mobile phone RF fields has been reported to increase the risk for neuroma and glioma [11]. The underlying reasons of these induced CNS disorders are largely unknown

Methods

Results

Conclusion