期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 15, 页码 -出版社
MDPI
DOI: 10.3390/ijms23158745
关键词
cytokines; lipopolysaccharide; oxylipins; circumventricular organs; immune-to-brain communication
资金
- EU Joint Programme -Neurodegenerative Disease Research (JPND) [SOLID JPND2021-650-233]
- Federal Ministry of Education and Research [01ED2207]
- Justus Liebig University
This study investigated the potential of sensory circumventricular organs (sCVOs) to produce n-3 and n-6 oxylipins after lipopolysaccharide (LPS) stimulation. The results showed that LPS stimulation increased the release of cytokines and certain oxylipins. However, co-treatment with norepinephrine (NE) did not significantly alter the levels of oxylipins or the changes in TNF alpha levels. These findings suggest that LPS-induced oxylipins may play an important role in immune-to-brain communication.
Sensory circumventricular organs (sCVOs) are pivotal brain structures involved in immune-to-brain communication with a leaky blood-brain barrier that detect circulating mediators such as lipopolysaccharide (LPS). Here, we aimed to investigate the potential of sCVOs to produce n-3 and n-6 oxylipins after LPS-stimulation. Moreover, we investigated if norepinephrine (NE) co-treatment can alter cytokine- and oxylipin-release. Thus, we stimulated rat primary neuroglial sCVO cultures under n-3- or n-6-enriched conditions with LPS or saline combined with NE or vehicle. Supernatants were assessed for cytokines by bioassays and oxylipins by HPLC-MS/MS. Expression of signaling pathways and enzymes were analyzed by RT-PCR. Tumor necrosis factor (TNF)alpha bioactivity and signaling, IL-10 expression, and cyclooxygenase (COX)2 were increased, epoxide hydroxylase (Ephx)2 was reduced, and lipoxygenase 15-(LOX) was not changed by LPS stimulation. Moreover, LPS induced increased levels of several n-6-derived oxylipins, including the COX-2 metabolite 15d-prostaglandin-J2 or the Ephx2 metabolite 14,15-DHET. For n-3-derived oxylipins, some were down- and some were upregulated, including 15-LOX-derived neuroprotectin D1 and 18-HEPE, known for their anti-inflammatory potential. While the LPS-induced increase in TNF alpha levels was significantly reduced by NE, oxylipins were not significantly altered by NE or changes in TNF alpha levels. In conclusion, LPS-induced oxylipins may play an important functional role in sCVOs for immune-to-brain communication.
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