Excretory–secretory products from Paragonimus westermani increase nitric oxide production in microglia in PKC-dependent and -independent manners
| Autor: | Youngnam N. Jin, In Young Choi, Won Ki Kim, Suyoung Hong, Chunsook Kim |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Paragonimiasis
MAP Kinase Signaling System p38 mitogen-activated protein kinases Nitric Oxide Synthase Type II Mitogen-activated protein kinase kinase Biology Nitric Oxide p38 Mitogen-Activated Protein Kinases Rats Sprague-Dawley Adenylyl cyclase chemistry.chemical_compound Central Nervous System Infections fluids and secretions Paragonimus westermani Cyclic AMP Animals Enzyme Inhibitors Phosphorylation Cyclic AMP Response Element-Binding Protein Protein kinase A Cells Cultured Protein Kinase C Protein kinase C Forskolin Kinase General Neuroscience JNK Mitogen-Activated Protein Kinases NF-kappa B Brain General Medicine biochemical phenomena metabolism and nutrition Cyclic AMP-Dependent Protein Kinases Protein Kinase A Inhibitor Rats Cell biology chemistry Encephalitis Microglia |
| Zdroj: | Neuroscience Research. 65:141-147 |
| ISSN: | 0168-0102 |
| DOI: | 10.1016/j.neures.2009.06.006 |
| Popis: | Excretory-secretory products (ESP) from helminthic parasites may play pivotal roles in the immune regulation in hosts. Previously, we reported that ESP produced from Paragonimus westermani induced morphological activation of microglial cells and markedly stimulated nitric oxide (NO) production via activation of mitogen-activated protein kinases (MAPKs). In the present study, we investigated the role of protein kinase C and protein kinase A in MAPKs-dependent NO production by ESP. We found that treatment with protein kinase C inhibitor Go6976 strongly inhibited the phosphorylation of p38 and JNK, but not ERK, of MAPKs and decreased the production of NO in ESP-stimulated microglial cells. Inhibition of ERK, p38 or PKC decreased the ESP-induced activation of NF-kappaB, an important transcription factor for iNOS expression. Furthermore, ESP increased the level of p-CREB in microglial cells. However, adenylyl cyclase activator (forskolin), adenylyl cyclase inhibitor (SQ22536), cAMP analogue (db-cAMP) or protein kinase A inhibitor (H89) was not able to change iNOS expression and NO production in ESP-treated microglial cells. It implies that the cAMP-PKA-CREB pathway is not implicated in the ESP-evoked NO production in microglial cells. Thus, our results indicate that ESP stimulates microglial expression of iNOS via both PKC-dependent and -independent MAPKs phosphorylation and NF-kappaB activation. |
| Databáze: | OpenAIRE |
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