Multiple sclerosis (MS) is a primary inflammatory demyelinating disease of the human central nervous system, characterized by accumulation of mononuclear cells of hematogenous origin. RANTES is a C-C (β)-chemokine family member with strong chemoattractant activity for lymphocytes and monocytes that are implicated in the pathogenesis of MS lesions. However, the cellular sources of RANTES message and the regulation of its secretion within diseased brain are poorly understood. Therefore, we carried out this study to compare the effect of Th1 cytokines on the induction of RANTES in different human astrocytic cell lines. IFN-γ alone had little effect on RANTES production in both U-373MG and U-105MG cells, while TNF-α or IL-1β alone had differential effects in the two cell lines. Low levels of RANTES chemokine were detected in culture supernatants from U-373MG cells. By contrast, TNF-α or IL-1β dramatically increased RANTES secretion in U-105MG cells. Interestingly, different combination treatments of cells with the three cytokines synergistically induced RANTES release from both U-373MG and U-105MG cells. Consistent with these results, we found similar expression patterns for RANTES at the comparable steady-state mRNA levels in both cell lines. Furthermore, we showed that U-105MG cells treated with TNF-α and IL-1β alone or in combination markedly induced increases in the rate of transcription of the RANTES chemokine gene. Our results indicate that these cell lines may be good model systems for studying the regulation of RANTES expression by cytokines in human glial cells.

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