Interplay between Matrix Metalloproteinase-9, Matrix Metalloproteinase-2, and Interleukins in Multiple Sclerosis
Alessandro Trentini1, Massimiliano Castellazzi2, Carlo Cervellati1
1Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Abstract:
Matrix Metalloproteases (MMPs) and cytokines have been involved in the pathogenesis of multiple sclerosis (MS). However, no studies have still explored the possible associations between the two families of molecules. The present study aimed to evaluate the contribution of active MMP-9, active MMP-2, interleukin- (IL-) 17, IL-18, IL-23, and monocyte chemotactic proteins-3 to the pathogenesis of MS and the possible interconnections between MMPs and cytokines. The proteins were determined in the serum and cerebrospinal fluid (CSF) of 89 MS patients and 92 other neurological disorders (OND) controls. Serum active MMP-9 was increased in MS patients and OND controls compared to healthy subjects (p < 0.001 and p < 0.01, resp.), whereas active MMP-2 and ILs did not change. CSF MMP-9, but not MMP-2 or ILs, was selectively elevated in MS compared to OND (p < 0.01). Regarding the MMPs and cytokines intercorrelations, we found a significant association between CSF active MMP-2 and IL-18 (r = 0.3, p < 0.05), while MMP-9 did not show any associations with the cytokines examined. Collectively, our results suggest that active MMP-9, but not ILs, might be a surrogate marker for MS. In addition, interleukins and MMPs might synergistically cooperate in MS, indicating them as potential partners in the disease process.
Insights
Active matrix metalloproteinase-9 (MMP-9) may serve as a biomarker for multiple sclerosis (MS). Interleukins and MMPs might interact, suggesting a synergistic role in MS pathogenesis.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
- Molecular Mechanisms of Disease
Background:
- Matrix metalloproteinases (MMPs) and cytokines are implicated in multiple sclerosis (MS) pathogenesis.
- Previous research has not explored the interplay between MMPs and cytokines in MS.
Purpose of the Study:
- To investigate the role of active MMP-9, MMP-2, IL-17, IL-18, IL-23, and MCP-3 in MS.
- To explore potential associations between MMPs and cytokines in MS.
Main Methods:
- Quantification of specific proteins in serum and cerebrospinal fluid (CSF) from 89 MS patients and 92 controls with other neurological disorders (OND).
- Analysis included active MMP-9, active MMP-2, IL-17, IL-18, IL-23, and MCP-3.
Main Results:
- Serum active MMP-9 was elevated in both MS and OND groups compared to healthy controls.
- CSF active MMP-9 was significantly higher in MS patients compared to OND controls.
- A positive correlation was observed between CSF active MMP-2 and IL-18 levels in MS patients.
Conclusions:
- Active MMP-9 may function as a potential biomarker for MS, independent of ILs.
- MMPs and interleukins may collaborate synergistically in the pathological processes of MS.
Related Concept Videos
Role of Matrix Metalloproteases in Degradation of ECM
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
The Extracellular Matrix
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
The Extracellular Matrix

