Related Experiment Video
Updated: Oct 1, 2026
Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
Published on: May 31, 2018
p38 mitogen-activated protein kinase mediates lipopolysaccharide, not interferon-gamma, -induced inducible nitric
Inn Oc Han1, Ki-Wan Kim, Jong Hoon Ryu
1Department of Pharmacology, College of Medicine, Ewha Institute of Neuroscience, Ewha Women's University, 70 Chongro-6-ga, Chongro-ku, Seoul 110-783, South Korea.
Abstract:
The present study examined the role of mitogen - activated protein kinases (MAPKs) in inducible nitric oxide synthase (iNOS) induction by lipopolysaccharide (LPS) or interferon - gamma (IFN - gamma) in the murine microglial cell line BV2 cells. LPS rapidly (<2 h) induced iNOS mRNA expression whereas IFN - gamma did not within 8 h after stimulation. LPS activated three MAPK subtypes, extracellular signal - regulated kinase (ERK), p38 and c - Jun N - terminal kinase (JNK) as early as 15 min after stimulation. In contrast, IFN - gamma activated only ERK after 6 h of stimulation and did not alter the activity of p38 and JNK. LPS-induced iNOS expression was markedly decreased by the p38 inhibitor SB203580, but not by the MAPK or ERK kinase inhibitor PD98059. IFN - gamma - induced nitric oxide (NO) generation was partially inhibited by PD98059 and SB203580 only in combination. The results demonstrate that MAPKs differentially mediate NO production by LPS - and IFN - gamma in BV2 cells.
Insights
Mitogen-activated protein kinases (MAPKs) differentially regulate nitric oxide production in BV2 cells stimulated by lipopolysaccharide (LPS) or interferon-gamma (IFN-γ). The p38 pathway is key for LPS-induced iNOS, while both ERK and p38 are involved in IFN-γ signaling.
Area of Science:
- Immunology
- Cell Biology
- Neuroscience
Background:
- Microglia play crucial roles in neuroinflammation.
- Inducible nitric oxide synthase (iNOS) is a key mediator of microglial inflammatory responses.
- Mitogen-activated protein kinases (MAPKs) are critical signaling pathways involved in cellular responses to stimuli.
Purpose of the Study:
- To investigate the distinct roles of MAPKs in iNOS induction by LPS and IFN-γ in BV2 microglial cells.
- To elucidate the specific MAPK pathways mediating nitric oxide (NO) production under different stimulation conditions.
Main Methods:
- BV2 cells were stimulated with LPS or IFN-γ.
- MAPK activation (ERK, p38, JNK) was assessed.
- iNOS mRNA expression and NO generation were measured.
- Specific MAPK inhibitors (SB203580, PD98059) were used to determine pathway involvement.
Main Results:
- LPS rapidly induced iNOS mRNA and activated ERK, p38, and JNK.
- IFN-γ induced iNOS later and primarily activated ERK.
- The p38 inhibitor SB203580 significantly reduced LPS-induced iNOS.
- Both PD98059 and SB203580 were required to partially inhibit IFN-γ-induced NO generation.
Conclusions:
- MAPKs play differential roles in mediating NO production by LPS and IFN-γ in BV2 cells.
- The p38 pathway is predominantly involved in LPS-induced iNOS, whereas both ERK and p38 pathways contribute to IFN-γ-induced NO production.
