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Inhibitory effect of meloxicam on human polymorphonuclear leukocyte adhesion to human synovial cell
Liang-cheng Li1, Qi Hou, Ying Guo
1Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Aim:
To investigate the effect of meloxicam on human polymorphonuclear leukocyte (PMN) adhesion to human synovial cell (HSC), and to explore its mechanism.
Methods:
MTT colorimetry was used to determine the adhesion effect of PMN to HSC. Cell-ELISA and RT-PCR methods were used to determine the expression of ICAM-1 and VCAM-1. Nuclear transcription factor-kappa B (NF-kappa B) was measured by electrophoretic mobility shift assay (EMSA) method.
Results:
Meloxicam was found to effectively inhibit TNF-alpha (50 u.mL-1 for 12 h) and IL-1 beta (50 u.mL-1 for 12 h)-induced adhesion of PMN to HSC (IC50 3.38 x 10(-7) mol.L-1 and 3.56 x 10(-6) mol.L-1, respectively) in a concentration-dependent manner. ICAM-1 protein and mRNA expression induced by TNF-alpha (50 u.mL-1) were inhibited by meloxicam at 1 x 10(-6)-1 x 10(-5) mol.L-1. The activation of NF-kappa B was also inhibited by meloxicam at 1 x 10(-6)-1 x 10(-5) mol.L-1.
Conclusion:
These results suggest that meloxicam inhibit TNF-alpha stimulated PMN-HSC adhesion and expression of ICAM-1 by suppressing the activity of NF-kappa B.
Insights
Meloxicam effectively inhibits polymorphonuclear leukocyte (PMN) adhesion to human synovial cells (HSC) by suppressing nuclear transcription factor-kappa B (NF-kappa B) activation and intercellular adhesion molecule-1 (ICAM-1) expression.
Area of Science:
- Immunology
- Pharmacology
- Biochemistry
Background:
- Polymorphonuclear leukocytes (PMNs) play a crucial role in inflammatory processes within the synovial environment.
- Synovial cell (HSC) interactions with PMNs contribute to joint inflammation and damage.
- Understanding the molecular mechanisms regulating PMN-HSC adhesion is vital for developing targeted anti-inflammatory therapies.
Purpose of the Study:
- To investigate the anti-inflammatory effects of meloxicam on human PMN adhesion to human synovial cells (HSC).
- To elucidate the underlying molecular mechanisms, including the role of intercellular adhesion molecule-1 (ICAM-1) and nuclear transcription factor-kappa B (NF-kappa B).
Main Methods:
- MTT colorimetry was employed to quantify PMN-HSC adhesion.
- Cell-ELISA and RT-PCR were utilized to assess the expression levels of ICAM-1 and VCAM-1.
- Electrophoretic mobility shift assay (EMSA) was performed to measure the activation of NF-kappa B.
Main Results:
- Meloxicam demonstrated a concentration-dependent inhibition of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta)-induced PMN-HSC adhesion.
- Meloxicam significantly reduced TNF-alpha-induced expression of ICAM-1 at both protein and mRNA levels.
- The drug effectively suppressed the activation of NF-kappa B in a concentration-dependent manner.
Conclusions:
- Meloxicam exhibits potent anti-adhesion properties in the context of PMN-HSC interactions.
- The mechanism involves the suppression of ICAM-1 expression and NF-kappa B activation.
- These findings highlight meloxicam's potential as a therapeutic agent for inflammatory joint conditions by modulating key inflammatory pathways.