Rat microglial cells secrete predominantly the precursor of interleukin-1 beta in response to lipopolysaccharide

Little is known on the forms of interieukin-1 beta (IL-1 beta) that are pro duced by microglial cells in the nervous system. Mixed glial cell cultures of rats produced IL-1 beta in response to lipopolysaccharide (LPS). Using W estern blot, pro-IL-1 beta was found to be localized both intracellularly a nd in the supernatant, whereas mature IL-1 beta was found only in the super natant but in lower quantities than pro-IL-1 beta. Immunocytochemistry conf irmed that microglial cells are the exclusive source of IL-1 beta. Blockade of the IL-1 beta -converting enzyme (ICE) by Tyr-Val-Ala-Asp-aldehyde (YVA D-CHO) decreased the levels of mature IL-1 beta but had no effect on pro-IL -1 beta. Release of pro-IL-1 beta was not associated with cell death nor wi th the extracellular release of ICE. Using gelatin zymography, glial cells were found to express constitutive matrix metalloproteinases (MMP) in the f orm of MMP-2. Exposure to LPS induced MMP-9 expression in a time-dependent manner similar to the pro-IL-1 beta expression profile. MMP activation and inhibition experiments indicated a possible role of MMPs in the cleavage of pro-IL-1 beta but not in the generation of mature IL-1 beta. Microglial ce lls share with macrophages the ability to release large amounts of pro-IL-1 beta of which the extracellular role remains to be determined.