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Relationship between metalloproteinase 2 and 9 concentrations and soluble CD154 expression in Iranian patients with
Javad Sanchooli1, Nourollah Ramroodi2, Nima Sanadgol3
1Department of Immunology, Zabol University of Medical Sciences, Zabol, Iran.
Abstract:
Matrix metalloproteinases (MMPs) play a critical role in the blood-brain barrier permeability and in invasion of the leukocytes into the central nervous system during multiple sclerosis (MS). In this respect, in the present study, we have evaluated the possible role of MMP-9 and MMP-2 on the expression of soluble CD154 (sCD154) and membrane-bound isoform of the CD154 in Iranian MS patients. The expressions of the aforementioned protein-related genes were analyzed at the levels of messenger RNA and proteins by real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. The results showed a high expression of CD154 isoforms, MMP-9 and MMP-2, in MS patients in contrast to controls (p < 0.001). We found an increase in sCD154 concentration (i.e., >3-fold) in patients with a higher MMPs/tissue inhibitor of metalloproteinase 1 (TIMP-1) ratio. Furthermore, secondary-progressive MS patients with exacerbate period showed higher positive correlation between increasing sCD154 concentration and overexpression of MMP-2 (p < 0.001). Our data demonstrate that following the exacerbation period, sCD154 concentration is increased in patients, which is mutually related to the MMPs/TIMP-1 ratio. This relationship may represent a new link between sCD154 concentration and the MMPs/TIMP-1 ratio with prognostic implications.
Insights
Matrix metalloproteinases (MMPs) and soluble CD154 (sCD154) are elevated in multiple sclerosis (MS) patients. Increased MMPs/TIMP-1 ratio correlates with higher sCD154, suggesting a new prognostic marker for MS.
Area of Science:
- Neuroimmunology
- Biochemistry
- Molecular Biology
Background:
- Matrix metalloproteinases (MMPs) are implicated in blood-brain barrier dysfunction and leukocyte invasion in multiple sclerosis (MS).
- CD154, in both soluble (sCD154) and membrane-bound forms, is involved in immune responses relevant to MS pathogenesis.
Purpose of the Study:
- To investigate the relationship between MMP-2, MMP-9, and CD154 isoforms in Iranian MS patients.
- To explore the potential role of the MMPs/tissue inhibitor of metalloproteinase 1 (TIMP-1) ratio in modulating sCD154 levels.
Main Methods:
- Gene and protein expression analysis using real-time RT-PCR, ELISA, and Western blotting.
- Quantification of MMP-2, MMP-9, and CD154 isoforms in MS patients and healthy controls.
- Correlation analysis between MMPs/TIMP-1 ratio and sCD154 concentration.
Main Results:
- Significantly higher expression of CD154 isoforms, MMP-2, and MMP-9 was observed in MS patients compared to controls (p < 0.001).
- A >3-fold increase in sCD154 concentration was associated with a higher MMPs/TIMP-1 ratio.
- Secondary-progressive MS patients during exacerbation showed a strong positive correlation between elevated sCD154 and MMP-2 overexpression (p < 0.001).
Conclusions:
- sCD154 concentration increases following MS exacerbation, correlating with the MMPs/TIMP-1 ratio.
- This interplay suggests a novel link between sCD154, MMPs/TIMP-1 ratio, and potential prognostic implications in multiple sclerosis.
- The findings highlight MMPs and sCD154 as potential biomarkers in MS progression.
