The role of cytosolic phospholipase A2 in microglial signaling pathways during neuroinflammation
type: CreativeWork
description: Oxidative and nitrosative stress is known to play an important role in neurodegenerative and neuroinflammatory diseases, such as Alzheimer's disease, Parkinson's disease, ischemic[slash]hemorrhagic stroke, and traumatic brain injury. Microglia are the primary innate immune cells in the central nervous system (CNS). These cells are the first line of defense against foreign pathogens, and the exhibit multiple physiological roles including removing cellular debris and maintaining tissue homeostasis. Pathologic activation of microglia, which is frequently secondary to neurodegenerative or neuroinflammatory processes, can lead to the release of proinflammatory cytokines, reactive oxygen species (ROS), reactive nitrogenous species (RNS), excitotoxic neurotransmitters, metalloproteases, and other pro-inflammatory[slash]cytotoxic factors. Propagation of inflammation in neurodegenerative conditions and can be a contributor of neuronal cell death. Cytosolic phospholipase A2 (cPLA2) belongs to a family of phospholipases that act as the principle producers of arachidonic acid (AA) in cells. During the process of inflammation, AA released from phospholipids is metabolized by cyclooxygenase-1[slash]2 (COX1[slash]2) and lipoxygenases, and in turn can be converted to prostaglandins, prostacyclin and thromboxane. This is an important pathway of inflammation, with COX1[slash]2 being the popular target for non-steroidal anti-inflammatory drugs (NSAIDs). The role of cPLA2 and its downstream pathway has not been investigated in depth in microglial cells during CNS neuroinflammation. Using primary microglial culture prepared from cPLA2 knockout mice, we found that oxidative and nitrosative stress responses were significantly attenuated in cPLA2 knockout mice as compared with wildtype control. The same phenomenon was observed using pharmacological inhibition and siRNA knockdown of cPLA2 in BV2 microglial cells. Interestingly, unlike macrophages, inhibition of COX1[slash]2 did not result i…
abstract: Oxidative and nitrosative stress is known to play an important role in neurodegenerative and neuroinflammatory diseases, such as Alzheimer's disease, Parkinson's disease, ischemic[slash]hemorrhagic stroke, and traumatic brain injury. Microglia are the primary innate immune cells in the central nervous system (CNS). These cells are the first line of defense against foreign pathogens, and the exhibit multiple physiological roles including removing cellular debris and maintaining tissue homeostasis. Pathologic activation of microglia, which is frequently secondary to neurodegenerative or neuroinflammatory processes, can lead to the release of proinflammatory cytokines, reactive oxygen species (ROS), reactive nitrogenous species (RNS), excitotoxic neurotransmitters, metalloproteases, and other pro-inflammatory[slash]cytotoxic factors. Propagation of inflammation in neurodegenerative conditions and can be a contributor of neuronal cell death. Cytosolic phospholipase A2 (cPLA2) belongs to a family of phospholipases that act as the principle producers of arachidonic acid (AA) in cells. During the process of inflammation, AA released from phospholipids is metabolized by cyclooxygenase-1[slash]2 (COX1[slash]2) and lipoxygenases, and in turn can be converted to prostaglandins, prostacyclin and thromboxane. This is an important pathway of inflammation, with COX1[slash]2 being the popular target for non-steroidal anti-inflammatory drugs (NSAIDs). The role of cPLA2 and its downstream pathway has not been investigated in depth in microglial cells during CNS neuroinflammation. Using primary microglial culture prepared from cPLA2 knockout mice, we found that oxidative and nitrosative stress responses were significantly attenuated in cPLA2 knockout mice as compared with wildtype control. The same phenomenon was observed using pharmacological inhibition and siRNA knockdown of cPLA2 in BV2 microglial cells. Interestingly, unlike macrophages, inhibition of COX1[slash]2 did not result i…
author: Chuang, Dennis Yi-Lun, 1985-
language: eng
language: English
date published: 2016
date modified: 2026-07-24T03:09:27Z
provider: University of Missouri
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Missouri--Columbia

PropertyValue
property ID: Handle
value: https://hdl.handle.net/10355/56462

PropertyValue
property ID: DOI
value: 10.32469/10355/56462