Gemfibrozil, a Lipid-lowering Drug, Induces Suppressor of Cytokine Signaling 3 in Glial Cells

Up-regulation of Ciliary Neurotrophic Factor in Astrocytes by Aspirin

“…Isolation of Primary Mouse Astroglia-Astroglia were isolated from 7-to 9-day-old old mouse pups as described earlier (17)(18)(19). Briefly, on day 9, the mixed glial cultures were subjected to shaking at 240 rpm for 2 h at 37°C on a rotary shaker to remove microglia followed by another round of shaking on day 11 at 190 rpm for 18 h to remove oligodendroglia and residual microglia.…”

Gemfibrozil and Fenofibrate, Food and Drug Administration-approved Lipid-lowering Drugs, Up-regulate Tripeptidyl-peptidase 1 in Brain Cells via Peroxisome Proliferator-activated Receptor α

“…Semi-quantitative RT-PCR was carried out as described earlier (24) using oligo(dT) [12][13][14][15][16][17][18] as primer and Moloney murine leukemia virus reverse transcriptase (Invitrogen) in a 20-l reaction mixture. The resulting cDNA was appropriately amplified using Promega Master Mix (Madison, WI) and the following primers (Invitrogen) for murine genes: mouse Cln1, sense 5Ј-ACACAGAGGACCGCCTGGGG-3Ј and antisense 5Ј-TCA-TGCACGGCCCACACAGC-3Ј; mouse Cln2, sense 5Ј-CAC-CATCCAGTTACTTCAATGC-3Ј and antisense 5Ј-CTGAC-CCTCCACTTCTTCATTC-3Ј; mouse Cln3, sense 5Ј-TGCTGC-CCTGCCATCGAGTG-3Ј and antisense 5Ј-GGCAGCGCTC-AGCATCACCA-3Ј; and mouse Gapdh, sense 5Ј-GCACAGT-CAAGGCCGAGAAT-3Ј and antisense 5Ј-GCCTTCTCCATG-GTGGTGAA-3Ј.…”

“…However, a number of recent studies reveal that apart from its lipid-lowering effects, these drugs, especially gemfibrozil, can also regulate many other signaling pathways responsible for inflammation, such as switching of T-helper cells, cell-to-cell contact, migration, and oxidative stress (13)(14)(15)(16). Here, we describe that both gemfibrozil and fenofibrate are capable of enhancing TPP1 in cultured neurons and glial cells and in vivo in the brain.…”

Redox Control of Microglial Function: Molecular Mechanisms and Functional Significance

“…Thus, the protein levels of SOCS1 and SOCS3 are drastically elevated in response not only to TNF but also to hydrogen peroxide (H 2 O 2 ) in Jurkat T cells and mouse splenocytes (218). With regard to microglia, electrophilic compounds such as a caffeamide derivative (163) and gemfibrozil (89) have been reported to exert anti-neuroinflammatory functions through induction of SOCS3. The role of SOCS in neuroinflammation has been studied mainly in the context of multiple sclerosis (MS) where they are proposed to be putative targets to modulate chronic inflammation (78).…”