Related Experiment Videos
Substance P augments nitric oxide production and gene expression in murine macrophages
1Department of Biology, Yonsei University, Seoul, South Korea. hkjeon@biology.yonsei.ac.kr
Abstract:
We investigated the effects of substance P (SP) on nitric oxide (NO) synthase activity in macrophages by measuring the production of nitrite and the expression of inducible NO synthase (iNOS) mRNA and protein. In LPS-activated macrophages, SP stimulated NO production in time and concentration dependent manners. These SP effects were blocked by a specific NK-1 receptor antagonist. Furthermore, SP stimulation increased the levels of both iNOS mRNA and iNOS protein. These results demonstrate that SP can increase LPS induced NO production in macrophages by augmenting the induction of iNOS expression. We also examined the role of SP on acute-cold stress induced altered production of NO by mouse peritoneal macrophages. SP enhanced the LPS-induced macrophages NO production from stressed mice relative to the non-stressed mice. These results suggest that SP may have an important modulatory role in production of NO by macrophages.
Insights
Substance P (SP) boosts nitric oxide (NO) production in macrophages by increasing inducible NO synthase (iNOS) expression. This effect is blocked by NK-1 receptor antagonists and is more pronounced in stressed conditions, suggesting SP modulates macrophage NO production.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Nitric oxide (NO) is a crucial signaling molecule involved in immune responses.
- Macrophages play a key role in innate and adaptive immunity.
- Substance P (SP) is a neuropeptide with known immunomodulatory functions.
Purpose of the Study:
- To investigate the effect of Substance P (SP) on nitric oxide (NO) synthase activity in macrophages.
- To determine the role of SP in regulating inducible NO synthase (iNOS) expression.
- To examine SP's influence on NO production in macrophages under stress conditions.
Main Methods:
- Macrophages were stimulated with lipopolysaccharide (LPS) and SP.
- Nitrite production was measured as an indicator of NO synthesis.
- Expression of iNOS mRNA and protein was quantified.
- An NK-1 receptor antagonist was used to assess receptor specificity.
Main Results:
- SP significantly stimulated NO production in LPS-activated macrophages in a dose- and time-dependent manner.
- The SP-induced NO production was inhibited by a specific NK-1 receptor antagonist.
- SP increased both iNOS mRNA and protein levels in macrophages.
- SP enhanced LPS-induced NO production in macrophages from cold-stressed mice.
Conclusions:
- Substance P augments lipopolysaccharide-induced NO production in macrophages by enhancing iNOS expression.
- The NK-1 receptor mediates the effects of SP on macrophage NO production.
- SP plays a modulatory role in NO production by macrophages, particularly under stress.