Effects of CCL2 on astrocytic mRNA expression: microarray analysis

Chemokines are involved in neuroinflammation and activate cells of the central nervous system (CNS) as well as leukocytes. Astrocytes are a primary source of chemokines in the brain. In addition, astrocytes also express chemokine receptors. Although, it is known that CCL2 induces several effects in astrocytes, the expression of its' primary receptor CCR2 is controversial. Recent evidence strongly suggests that CCL2 activates an alternative receptor called HCR in human astrocytes. The aim of the present study was to investigate the effect of CCL2-induced activation of HCR on the regulation of gene expression in human adult astrocytes using microarray assays. Surprisingly, we observed a reduction in expression of genes that belong to the family of metalloproteinases (MMPs). Subsequent RT-PCR and preliminary Q-PCR studies confirmed the microarray data and showed down regulation of MMP2, MMP14, MMP16 and the regulators of MMPs, TIMP1 and TIMP2 after prolonged stimulation with CCL2 in astrocytes. Since MMPs are important mediators in neuroinflammation and are involved in the mechanism underlying infiltration of leukocytes in the CNS, we suggest that CCL2 induces anti-inflammatory activity in astrocytes.