Induction of interleukin-1beta by interleukin-4 in lipopolysaccharide-treated mixed glial cultures: microglial-dependent effects |
| |
Authors: | Cao Ling Fei Liang Chang Tina Ting-Lan DeLeo Joyce A |
| |
Affiliation: | Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA. |
| |
Abstract: | Glial-secreted proinflammatory mediators are dynamically involved in central nervous system responses to exogenous stimuli such as infection, neurotoxins, and nerve injury. The therapeutic use of anti-inflammatory agents may reduce certain central nervous system pathology induced by inflammatory responses. We investigated the role of interleukin (IL)-4 in modulating the production of proinflammatory mediators from lipopolysaccharide-stimulated mixed glia in vitro. Interestingly, IL-4 significantly enhanced IL-1beta secretion and did not affect monocyte chemoattractant protein-1 release, even though IL-4 considerably inhibited IL-6, tumor necrosis factor alpha, and nitric oxide production from rat neonatal mixed glia. Further, IL-4 exhibited inhibitory effects on IL-1beta production in microglial-enriched cultures, while significantly increasing IL-1beta production in microglial-depleted glia. The enhancing effect of IL-4 on IL-1beta production was found to be inversely correlated with the percentage of microglia present in the mixed glial population. In summary, IL-4 did not act as a global anti-inflammatory cytokine and in fact, under certain situations enhanced IL-1beta secretion. We conclude that IL-4 exerts its anti-inflammatory effects in a limited and target-specific manner, which is delicately regulated by the cellular microenvironment. Therefore, precaution should be taken when clinically using IL-4 to treat diseases manifested by overt inflammatory responses. |
| |
Keywords: | adult glial culture interleukin-1β interleukin-4 lipopolysaccharide microglia monocyte chemoattractant protein-1 |
本文献已被 PubMed 等数据库收录! |
|