Bacterial lipopolysaccharide selectively up-regulates the function of the chemotactic peptide receptor formyl peptide receptor 2 in murine microglial cells
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Published on: May 31, 2018
You-Hong Cui1, Yingying Le, Wanghua Gong
1Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute, Building 560, Frederick, MD 21702, USA.
Abstract:
Receptors for the bacterial chemotactic peptide fMLP are implicated in inflammation and host defense against microbial infection. We investigated the expression and function of fMLPR in microglial cells, which share characteristics of mononuclear phagocytes and play an important role in proinflammatory responses in the CNS. The expression of the genes encoding formyl peptide receptor (FPR)1 and FPR2, the high- and low-affinity fMLPR, was detected in a murine microglial cell line N9, but these cells did not respond to chemotactic agonists known for these receptors. N9 cells incubated with bacterial LPS increased the expression of fMLPR genes and developed a species of specific, but low-affinity, binding sites for fMLP, in association with marked calcium mobilization and chemotaxis responses to fMLP in a concentration range that typically activated the low-affinity receptor FPR2. In addition, LPS-treated N9 cells were chemoattracted by two FPR2-specific agonists, the HIV-1 envelope-derived V3 peptide, and the 42 aa form of the amyloid beta peptide which is a pathogenic agent in Alzheimer's disease. Primary murine microglial cells also expressed FPR1 and FPR2 genes, but similar to N9 cells, exhibited FPR2-mediated activation only after LPS treatment. In contrast to its effect on the function of FPR2, LPS reduced N9 cell binding and biological responses to the chemokine stromal cell-derived factor-1alpha. Thus, LPS selectively modulates the function of chemoattractant receptors in microglia and may promote host response in inflammatory diseases in the CNS.
Insights
Bacterial peptide receptors (fMLPR) are activated in microglia after LPS treatment, enhancing inflammatory responses in the central nervous system (CNS). This study reveals selective modulation of microglial chemoattractant receptor function.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key immune cells in the CNS, crucial for inflammatory responses.
- Formyl peptide receptors (fMLPR) mediate responses to bacterial peptides and are involved in host defense.
- The role and regulation of fMLPR in microglial cells remain incompletely understood.
Purpose of the Study:
- To investigate the expression and function of formyl peptide receptors (fMLPR) in microglial cells.
- To determine how bacterial lipopolysaccharide (LPS) affects fMLPR expression and function in microglia.
- To explore the potential role of fMLPR in neuroinflammation and CNS diseases.
Main Methods:
- Utilized a murine microglial cell line (N9) and primary murine microglial cells.
- Assessed gene expression of formyl peptide receptor (FPR)1 and FPR2.
- Measured calcium mobilization, chemotaxis, and receptor binding in response to fMLP and specific agonists.
- Investigated the effect of LPS treatment on receptor function.
Main Results:
- N9 cells and primary microglia express FPR1 and FPR2, but show limited response without LPS.
- LPS treatment upregulated fMLPR gene expression and induced functional responses to fMLP, particularly via FPR2.
- LPS-induced microglial chemotaxis was observed towards FPR2 agonists, including amyloid-beta peptide.
- LPS selectively modulated chemoattractant receptor function, reducing responses to stromal cell-derived factor-1alpha.
Conclusions:
- Microglial formyl peptide receptor (fMLPR) function is selectively modulated by LPS, enhancing responses to bacterial peptides and other agonists.
- This LPS-induced activation of fMLPR in microglia may contribute to host defense and inflammatory processes in the CNS.
- Findings suggest a mechanism by which microglia contribute to neuroinflammation and host defense in response to microbial stimuli.
