Transforming growth factor β 1 prevents IL-1β-induced microglial activation, whereas TNFα- and IL-6-stimulated activation are not antagonized

Basu, Anirban ; Krady, J. Kyle ; Enterline, Jonathan R. ; Levison, Steven W. (2002) Transforming growth factor β 1 prevents IL-1β-induced microglial activation, whereas TNFα- and IL-6-stimulated activation are not antagonized Glia, 40 (1). pp. 109-120. ISSN 0894-1491

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Official URL: http://doi.org/10.1002/glia.10118

Related URL: http://dx.doi.org/10.1002/glia.10118

Abstract

Microglia rapidly respond to CNS injury, yet the mechanisms leading to their activation and inactivation remain poorly defined. In particular, few studies have established how interactions between inflammatory mediators affect the innate immune response of microglia. To begin to establish how microglia integrate signals from multiple inflammatory mediators, we examined the effects of interleukin 1β (IL‐1β), interleukin 6 (IL‐6), tumor necrosis factor α (TNFα), interferon γ (IFN‐γ), and transforming growth factor β1 (TGFβ1) on both newborn and bulk‐isolated adult microglia. To assess the functional state of the cells, we assayed the expression of cyclooxygenase 2 (Cox‐2), interleukin 6, and tumor necrosis factor α, and two protein tyrosine kinases that have been implicated in microglial responses to activational stimuli, HCK and FAK. These studies demonstrated that IL‐1β, TNFα, IL‐6, but not IFN‐γ increase the expression of Cox‐2, whereas they all increase the expression of HCK and FAK. In these studies, TGFβ1 either had no effect, or it decreased basal levels of these proteins. TGFβ1 blocked activation by IL‐1β when given prior to, or simultaneously with, IL‐1β. TGFβ1 blocked the induction of the tyrosine kinases, Cox‐2, and the induction of IL‐6 and TNFα mRNAs. However, TGFβ1 was ineffective in antagonizing the induction of Cox‐2 by either IL‐6 or TNFα. We conclude that the TGFβ receptor signaling cascades intersect with IL‐1, but they may not interact with IL‐6 or TNFα signaling pathways that lead to activation.

Item Type:Article
Source:Copyright of this article belongs to John Wiley & Sons.
Keywords:Cytokines; Rats; Tgfβ; Ifn‐γ; Brain Injury; Prostaglandins.
ID Code:115687
Deposited On:18 Mar 2021 04:48
Last Modified:19 Mar 2021 12:12

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