Astrocytes stimulate interleukin‐17 and interferon‐γ production in vitro

Abstract

Astrocytes play important roles in the complex and as yet not very well understood net of interactions among resident and infiltrating cells during central nervous system (CNS) inflammation. In such an intricate network, cytokines represent an essential means for intercellular communication, and astrocytes are able to affect their generation and/or release. Among various cytokines produced by infiltrating cells, interferon (IFN)-gamma and interleukin (IL)-17 are the focus of this research, because they are pivotal cytokines of helper T-cell type 1 (Th1) and helper T-cell type 17 (Th17), respectively. Importantly, both Th1 and Th17 cells, as well as their cytokines, have been shown to be of importance for the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of a prototypical CNS disease with inflammatory pathogenesis, multiple sclerosis. Therefore, the influence of astrocytes on the generation of IFN-gamma and IL-17 in concanavalin A- and myelin basic protein-stimulated lymph node cells of healthy rats and rats with developing EAE, respectively, was investigated in vitro. Astrocytes up-regulated IL-17 and IFN-gamma gene expression and protein synthesis in T cells, which coincided with astrocytes' ability to express IL-23 subunit p19 and common IL-12/IL-23 subunit p40 but not IL-12 subunit p35 in the co-cultivations. These results suggest one more way in which astrocytes could contribute to the complex interactions during CNS inflammation.

Astrocytes in the tempest of multiple sclerosis

“…Interestingly, while both rodent macrophages and astrocytes express iNOS in response to IFN-c, only astrocytes respond by further elevation of NO production in response to simultaneous stimulation with IFN-c and IL-17 [80]. Also, rat astrocytes are capable of stimulating both IFN-c and IL-17 synthesis in T cells [81]. Furthermore, astrocytic iNOS has been demonstrated in MS lesions, and it is recognized as an important pathogenic feature of MS [82].…”

“…Furthermore, astrocytic iNOS has been demonstrated in MS lesions, and it is recognized as an important pathogenic feature of MS [82]. [57,61,81,[83][84][85][86][87]. Thus, astrocytes could be involved in the complexity of cytokine functions in MS pathogenesis [88].…”

The Role of Cytokines in the Regulation of Neurotransmission

“…For instance, studies conducted in vitro have documented that fetal rat dorsal root ganglion neurons produce IFN-␥ and express its receptor [27,28] . The presence of astrocytes up-regulates IL-17 and IFN-␥ gene expression and protein synthesis in T cells, which is in line with the ability of astrocytes to express IL-23 subunit p19 and common IL-12/IL-23 subunit p40, but not IL-12 subunit p35 in co-cultures [29] . These results suggest that astrocytes contribute to the complex interactions during CNS inflammation by different mechanisms [29] .…”

“…The presence of astrocytes up-regulates IL-17 and IFN-␥ gene expression and protein synthesis in T cells, which is in line with the ability of astrocytes to express IL-23 subunit p19 and common IL-12/IL-23 subunit p40, but not IL-12 subunit p35 in co-cultures [29] . These results suggest that astrocytes contribute to the complex interactions during CNS inflammation by different mechanisms [29] . Moreover, cultured neurons from sympathetic and sensory ganglia express IL-6 mRNA and protein [30,31] .…”

Molecular Mechanism of MiR-136-5p Targeting NF-κB/A20 in the IL-17-Mediated Inflammatory Response after Spinal Cord Injury

“…Once astrocytes are activated, a substantial number of inflammatory mediators, such as NO, PGE2, excitatory amino acids, ATP and cytokines, such as IL-1β, TNF-a, and IL-6, will be released. These mediators of inflammation further activate glial cells, as well as the corresponding receptors in neurons, to enhance neuronal activity [19-21]. In the early stages of SCI, isolating the injury to stimulate and regulate the inflammatory response to maintain the stability of the local environment works as a protective barrier; however, when it develops in the later stages of an SCI, AS proliferates and leads to hypertrophy, which results in a substantial number of overlapping cells.…”