Astrogliosis is delayed in type 1 interleukin-1 receptor-null mice following a penetrating brain injury

Hsiao-Wen Lin,Michael Cicchese,Steven W Levison,Charles Druckman,J Kyle Krady,Anirban Basu

doi:10.1186/1742-2094-3-15

Abstract

The cytokines IL-1α and IL-1β are induced rapidly after insults to the CNS, and their subsequent signaling through the type 1 IL-1 receptor (IL-1R1) has been regarded as essential for a normal astroglial and microglial/macrophage response. To determine whether abrogating signaling through the IL-1R1 will alter the cardinal astrocytic responses to injury, we analyzed molecules characteristic of activated astrocytes in response to a penetrating stab wound in wild type mice and mice with a targeted deletion of IL-1R1. Here we show that after a stab wound injury, glial fibrillary acidic protein (GFAP) induction on a per cell basis is delayed in the IL-1R1-null mice compared to wild type counterparts. However, the induction of chondroitin sulfate proteoglycans, tenascin, S-100B as well as glutamate transporter proteins, GLAST and GLT-1, and glutamine synthetase are independent of IL-1RI signaling. Cumulatively, our studies on gliosis in the IL-1R1-null mice indicate that abrogating IL-1R1 signaling delays some responses of astroglial activation; however, many of the important neuroprotective adaptations of astrocytes to brain trauma are preserved. These data recommend the continued development of therapeutics to abrogate IL-1R1 signaling to treat traumatic brain injuries. However, astroglial scar related proteins were induced irrespective of blocking IL-1R1 signaling and thus, other therapeutic strategies will be required to inhibit glial scarring.

Highlights

IntroductionThe cytokines interleukin-1α and interleukin-1β (collectively referred to as IL-1) are dramatically and rapidly induced following injury to the CNS and elevated IL-1 levels are associated with many neurodegenerative diseases [1]
The cytokines interleukin-1α and interleukin-1β are dramatically and rapidly induced following injury to the CNS and elevated IL-1 levels are associated with many neurodegenerative diseases [1]
We examined the expression of the protease-activated receptor 1 (PAR-1) in wild type (WT) and IL-1R1-null mice following a neocortical penetrating injury as this receptor has been implicated in astrocyte hyperplasia after brain injury [41]

Summary

Introduction

The cytokines interleukin-1α and interleukin-1β (collectively referred to as IL-1) are dramatically and rapidly induced following injury to the CNS and elevated IL-1 levels are associated with many neurodegenerative diseases [1]. IL-1 subsequently increases the production of inflammatory mediators, such as cyclooxygenase 2, prostanoids, nitric oxide, matrix metalloproteinases, collagenase [17], and pro-inflammatory cytokines, including Interleukin-6 (IL-6) [18,19], tumor necrosis factor alpha (TNF-α) [20], colony stimulating factors [21] as well as itself. These molecules subsequently establish a feedforward cycle of inflammation [6]

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Discussion

Conclusion