Analysis of IL-6/gp130 family receptor expression reveals that in contrast to astroglia, microglia lack the oncostatin M receptor and functional responses to oncostatin M.

Abstract

The interleukin (IL)-6/gp130 family of cytokines (e.g., IL-6, IL-11, leukemia inhibitory factor (LIF) and oncostatin M (OSM)) play important roles in the central nervous system (CNS) during neuroinflammation and neurodevelopment. However, little is known regarding the responses by astroglia and microglia to this family of cytokines. Here the expression of the IL-6/gp130 cytokine receptors and subsequent signal pathway activation was examined in murine astrocytes and microglia in vitro. Astrocytes had high levels of OSMR mRNA while lower levels of IL-6R, LIFR and IL-11R mRNAs were also present. In comparison, in microglia there was no detectable OSMR mRNA, higher levels of IL-6R mRNA and lower levels of the LIFR and IL-11R mRNAs. The OSMR protein was present in astrocytes but was undetectable in microglia. Conversely, the IL-6R protein was present in microglia but not detectable in astrocytes. In astrocytes but not microglia, phosphorylation of STAT1 and STAT3 occurred in response to OSM, whereas both microglia and astrocytes responded to hyper-IL-6 (IL-6 linked to the soluble IL-6 receptor). Finally, in both microglia and astrocytes, OSM failed to activate NFκB or induce iNOS and nitrite production. We conclude: (1) notable differences exist in the expression of receptors utilized by the IL-6/gp130 family of cytokines in astrocytes and microglia, and (2) the findings provide a molecular basis for the differential response to OSM by astrocytes versus microglia and demonstrate a fundamental means for achieving cellular specificity in the response of these glial cells to this cytokine.