| Autor: |
Silwal, Ashok, House, Austin, Sandoval, Karin, Vijeth, Shaluah, Umbaugh, David, Crider, Albert, Mobayen, Shirin, Neumann, William, Witt, Ken A. |
| Předmět: |
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| Zdroj: |
Neurochemical Research; Mar2022, Vol. 47 Issue 3, p768-780, 13p |
| Abstrakt: |
Somatostatin receptor subtype 4 (SSTR4) is expressed in BV2 microglia, suggesting that SSTR4 agonists may impact microglia function. This study assessed the high-affinity SSTR4 agonist SM-I-26 (SMI) (0 nM, 10 nM, 1000 nM) against lipopolysaccharide (LPS)-induced inflammation (0, 10 or 100 ng/ml) over 6 or 24 h in BV2 microglia. Cell viability, nitrite output and mRNA expression changes of genes associated with our target (Sstr4), inflammation (Tnf-α, Il-6, Il-1β, inos), anti-inflammatory and anti-oxidant actions (Il-10, Catalase), and mediators of Aβ binding/phagocytosis (Msr1, Cd33, Trem1, Trem2) were measured. At 6 h SMI showed no effect across all conditions. At 24 h SMI (10 and 1000 nM) upregulated Sstr4 expression under inflammatory and non-inflammatory conditions. At 24 h SMI downregulated expression of the inflammatory cytokines Tnf-α (1000 nM within all LPS concentrations) and Il-6 (10 nM within 0 and 10 ng/ml LPS). At 24 h 10 nM SMI upregulated Il-10, while 1000 nM upregulated Catalase under inflammatory and non-inflammatory conditions. At 24 h Msr1 and Cd33 were upregulated by 1000 nM SMI under non-inflammatory conditions, while Trem1 was downregulated by 10 and 1000 nM SMI under mildly inflammatory and non-inflammatory conditions. These results show that SMI had concentration and time-dependent effects on mRNA expression of genes associated with different states of microglial activation. The SMI reduced Tnf-α and Il-6 inflammatory gene expression, and increased Il-10 anti-inflammatory gene expression, identifies anti-inflammatory actions of SSTR4 agonists extend to microglia. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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