Anti-Inflammatory Effects by Pharmacological Inhibition or Knockdown of Fatty Acid Amide Hydrolase in BV2 Microglial Cells
Fatty acid amide hydrolase (FAAH) has been recognized as a therapeutic target for several neurological diseases because its inhibition can exert neuroprotective and anti-inflammatory effects by boosting the endogenous levels of <i>N</i>-acylethanolamines. However, previous studies have s...
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MDPI AG
2019-05-01
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| Online Access: | https://www.mdpi.com/2073-4409/8/5/491 |
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| author | Mikiei Tanaka Kazuya Yagyu Scott Sackett Yumin Zhang |
| author_facet | Mikiei Tanaka Kazuya Yagyu Scott Sackett Yumin Zhang |
| author_sort | Mikiei Tanaka |
| collection | DOAJ |
| description | Fatty acid amide hydrolase (FAAH) has been recognized as a therapeutic target for several neurological diseases because its inhibition can exert neuroprotective and anti-inflammatory effects by boosting the endogenous levels of <i>N</i>-acylethanolamines. However, previous studies have shown inconsistent results by pharmacological inhibition and genetic deletion of FAAH in response to inflammation. In this study we used two inhibitors, PF3845 and URB597, together with siRNA knockdown to characterize further the effects of FAAH inhibition in BV2 microglial cells. Treatment with PF3845 suppressed lipopolysaccharide (LPS)-induced prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) production, and down-regulated cyclooxygenase-2 and microsomal PGE synthase. PF3845 reduced the expression of pro-inflammatory cytokines but had no effect on the expression of anti-inflammatory cytokines. The anti-inflammatory effects of URB597 were not as potent as those of PF3845. Knockdown of FAAH also suppressed PGE<sub>2</sub> production and pro-inflammatory gene expression. Interestingly, FAAH knockdown enhanced expression of anti-inflammatory molecules in both the absence and presence of LPS treatment. The anti-inflammatory effects of FAAH inhibition and knockdown were not affected by the cannabinoid receptor antagonists or the peroxisome proliferator-activated receptor (PPAR) antagonists. Although inhibition and knockdown of FAAH have potent anti-inflammatory effects and possibly lead to the dynamic change of microglial gene regulation, the underlying mechanisms remain to be elucidated. |
| first_indexed | 2024-03-12T07:04:35Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:04:35Z |
| publishDate | 2019-05-01 |
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| spelling | doaj.art-e31d67ad62ac4fab8d908966dfde0ef62023-09-02T23:32:46ZengMDPI AGCells2073-44092019-05-018549110.3390/cells8050491cells8050491Anti-Inflammatory Effects by Pharmacological Inhibition or Knockdown of Fatty Acid Amide Hydrolase in BV2 Microglial CellsMikiei Tanaka0Kazuya Yagyu1Scott Sackett2Yumin Zhang3Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814, USADepartment of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814, USADepartment of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814, USADepartment of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814, USAFatty acid amide hydrolase (FAAH) has been recognized as a therapeutic target for several neurological diseases because its inhibition can exert neuroprotective and anti-inflammatory effects by boosting the endogenous levels of <i>N</i>-acylethanolamines. However, previous studies have shown inconsistent results by pharmacological inhibition and genetic deletion of FAAH in response to inflammation. In this study we used two inhibitors, PF3845 and URB597, together with siRNA knockdown to characterize further the effects of FAAH inhibition in BV2 microglial cells. Treatment with PF3845 suppressed lipopolysaccharide (LPS)-induced prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) production, and down-regulated cyclooxygenase-2 and microsomal PGE synthase. PF3845 reduced the expression of pro-inflammatory cytokines but had no effect on the expression of anti-inflammatory cytokines. The anti-inflammatory effects of URB597 were not as potent as those of PF3845. Knockdown of FAAH also suppressed PGE<sub>2</sub> production and pro-inflammatory gene expression. Interestingly, FAAH knockdown enhanced expression of anti-inflammatory molecules in both the absence and presence of LPS treatment. The anti-inflammatory effects of FAAH inhibition and knockdown were not affected by the cannabinoid receptor antagonists or the peroxisome proliferator-activated receptor (PPAR) antagonists. Although inhibition and knockdown of FAAH have potent anti-inflammatory effects and possibly lead to the dynamic change of microglial gene regulation, the underlying mechanisms remain to be elucidated.https://www.mdpi.com/2073-4409/8/5/491immune cellscentral nervous system<i>N</i>-acylethanolaminesiRNAserine hydrolase |
| spellingShingle | Mikiei Tanaka Kazuya Yagyu Scott Sackett Yumin Zhang Anti-Inflammatory Effects by Pharmacological Inhibition or Knockdown of Fatty Acid Amide Hydrolase in BV2 Microglial Cells Cells immune cells central nervous system <i>N</i>-acylethanolamine siRNA serine hydrolase |
| title | Anti-Inflammatory Effects by Pharmacological Inhibition or Knockdown of Fatty Acid Amide Hydrolase in BV2 Microglial Cells |
| title_full | Anti-Inflammatory Effects by Pharmacological Inhibition or Knockdown of Fatty Acid Amide Hydrolase in BV2 Microglial Cells |
| title_fullStr | Anti-Inflammatory Effects by Pharmacological Inhibition or Knockdown of Fatty Acid Amide Hydrolase in BV2 Microglial Cells |
| title_full_unstemmed | Anti-Inflammatory Effects by Pharmacological Inhibition or Knockdown of Fatty Acid Amide Hydrolase in BV2 Microglial Cells |
| title_short | Anti-Inflammatory Effects by Pharmacological Inhibition or Knockdown of Fatty Acid Amide Hydrolase in BV2 Microglial Cells |
| title_sort | anti inflammatory effects by pharmacological inhibition or knockdown of fatty acid amide hydrolase in bv2 microglial cells |
| topic | immune cells central nervous system <i>N</i>-acylethanolamine siRNA serine hydrolase |
| url | https://www.mdpi.com/2073-4409/8/5/491 |
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