Regulation of GDNF expression in cultured astrocytes by inflammatory stimuli

Abstract

Astrocytes express increased levels of neurotrophic factors in response to pathological conditions in the CNS such as injury and inflammation. We have examined the effects of lipopolysaccharide (LPS) and inflammatory cytokines on the expression of GDNF by mouse astrocytes and by C6 glial cells. LPS and tumor necrosis factor-alpha (TNF-alpha) induced an increase in level of glial-derived neurotrophic factor (GDNF) mRNA in both cell types. Similarly, the synthesis of GDNF protein was increased by both treatments. Interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) induced similar effects on GDNF production, whereas IL-2 and IL-6 had no significant effects. These results indicate that the expression of GDNF in astrocytes is regulated by inflammatory stimuli and therefore may provide neurotrophic support to injured neurons in inflammatory conditions in the CNS.

Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury

“…TNF-␣ has been shown to increase the spontaneous synaptic currents in hippocampal neurons in vitro, suggestive of a role for TNF-␣ in mediating synaptic plasticity in vivo (65). TNF-␣ may also enhance the recovery process by increasing the expression of antiinflammatory cytokines, such as IL-10 and TGF-␣ (66), and this cytokine network may potentially play a role in chronic central nervous system repair mechanisms by triggering proliferative responses of astrocytes after injury (67)(68)(69).…”

Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity

“…19 In other tissues, an increase in the population of T cells or cytokines has been shown to upregulate the expression of neurotrophins, such as nerve growth factor (NGF), BDNF and NT-3, as well as GDNF. [30][31][32] The relationship between inflammatory reactions and production of growth factors has been demonstrated in a variety of systems and species as well as in cultured cells. 33,34 We speculate that the immune response due to Ad.LacZ might elevate the level of growth factors in the inner ear, leading to the protection of hair cells against aminoglycoside-induced ototoxicity.…”

Driving GDNF expression: The green and the red traffic lights

“…Indeed, elevated GDNF expression is observed in response to lipopolysaccharide (LPS) and to the proinflammatory cytokines IL-1b, IL-6, tumor necrosis factor (TNF)-a and TNF-b in C6 cells (Appel et al, 1997;Verity et al, 1998) and in U-87MG glioblastoma cells . In cultured astrocytes both exogenous TNF-a, via TNF receptors, and endogenously produced TNF-a induce GDNF expression, suggesting that an autocrine loop contributes to the production of neurotrophic factors in response to inflammation (Kuno et al, 2006).…”

“…Conflict might arise when comparing the positive impact of IL1b on GDNF levels in glial cell lines (Appel et al, 1997;Verity et al, 1998Verity et al, , 1999, or in mouse astrocyte cell cultures prepared from neonatal cortices (Appel et al, 1997), with the lack of effect of IL-1b on GDNF expression in striatal astrocyte cultures or when injected intrastriatally in mice (Ho and Blum, 1997). In line with this, data from our group indicates that IL-1b is not involved in GDNF upregulation in striatal cultures exposed to conditioned medium from H 2 O 2 -or L-DOPA-challenged substantia nigra neuron-glia cultures (unpublished results), whereas we have shown that IL-1b mediates GDNF up-regulation in substantia nigra cell cultures in response to H 2 O 2 or L-DOPA (Saavedra et al, 2007).…”