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Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Implications of the Matrix Metalloproteinases, Their Tissue Inhibitors and Some Other Inflammatory Mediators
Aldona Wierzbicka-Rucińska1, Izabela Kubiszewska2, Renata Grzywa-Czuba3
1Department of Biochemistry & Experimental Medicine, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.
Insights
In obese children, increased TIMP-1 and decreased MMP-2 expression in leukocytes suggest a compensatory response. Plasma markers also showed changes, with negative correlations between TIMP-2 and liver/fat inflammation markers.
Area of Science:
- Biochemistry
- Immunology
- Pediatrics
Background:
- Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are crucial in biological processes like adipogenesis and inflammation.
- Leukocyte infiltration into adipose tissue contributes to obesity-related inflammation and mediator production.
Purpose of the Study:
- To investigate MMPs, TIMPs, and inflammatory mediators in leukocytes and plasma of children with simple obesity.
- To identify associations between these factors and obesity-related phenotypes.
Main Methods:
- Analysis of leukocyte mRNA expression (MMP-2, -9, -12, -14, TIMP-1, -2, IL-6) using real-time quantitative PCR.
- Measurement of plasma MMP-9/TIMP-1, MMP-2/TIMP-2 ratios, and concentrations of MMP-9, TIMP-1, IL-1β, IL-6, TNF-α, leptin, and resistin via ELISA.
- Assessment of leukocyte MMPs activity using gelatin zymography.
Main Results:
- Obese children exhibited increased leukocyte TIMP-1, a trend of elevated MMP-9, and decreased MMP-2 expression.
- Plasma analysis revealed elevated MMP-9, leptin, and MMP9/TIMP1 ratio, alongside reduced TNF-α and MMP-2/TIMP-2 ratio.
- Negative correlations were observed between TIMP-2 and liver/fat inflammatory markers, and between leptin and ALT, MMP-9 and total cholesterol.
Conclusions:
- Early stages of childhood obesity may involve compensatory mechanisms, indicated by increased TIMP-1 and decreased MMP-2.
- Observed changes in plasma markers and negative correlations suggest a complex interplay between MMPs, TIMPs, and inflammatory processes in pediatric obesity.
Objectives:
Matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endo-peptidases engaged in many biological processes including adipogenesis, angiogenesis, and tissue remodeling. Fat tissue infiltration by peripheral leukocytes plays an important role in transition of fat tissue residual, non-inflammatory status into the pro-inflammatory one, resulting in fat tissue inflammation and expansion as well as production of many mediators like adipokines and cytokines. The aim of this study was to investigate the expression of MMPs, their endogenous tissue inhibitors (TIMPs), and selected inflammatory mediators in leukocytes and plasma of children with simple obesity to find their associations with obesity-related phenotypes.
Material And Methods:
Twenty-six overweight/obese children and twenty-three healthy volunteers participated in the study. The leukocyte mRNA expression levels of MMP-2, -9, -12 -14, TIMP-1, -2, and IL-6 were analyzed by the real time quantitative PCR. Plasma MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios as well as the concentrations of MMP-9, TIMP-1, IL-1 beta, IL-6, TNF- alpha, leptin and resistin were tested by ELISA assays. Gelatin zymography was used to assess the activity of the leukocyte MMPs proteins.
Results:
The obese children showed the following: a) increased expression of leukocyte TIMP-1 and slight elevation (close to statistical significance) of leukocyte MMP-9 (p = 0.054), the decline in MMP-2, b) elevation of plasma MMP-9, leptin, and MMP9/TIMP1 ratio, c) reduced expression of plasma TNF-alpha and MMP-2/TIMP-2 ratio. Several negative correlations were found: TIMP2 vs. ALT (r = -0.536), AST (r = -0.645) and TTG (r = -0.438), IL-6 vs. GGTP (r = -0.815), and MMP12 vs. TTG (r = -0.488), leptin vs. ALT (r = -0.569), MMP-9 vs. total cholesterol (r = -0.556). The only positive correlation was that of plasma leptin level vs. GGTP (r = 0.964).
Conclusions:
At the beginning of obesity development (children), possibly compensatory reactions prevail, reflected here by an increase in the expression of leukocyte MMPs inhibitor TIMP-1, decrease in the level of leukocyte MMP-2 and plasma MMP-2, MMP2/TIMP-2 ratio, low plasma TNF-alpha and negative correlations between the expression of TIMP-2 and liver (AST, ALT) or fat (TTG) inflammatory markers.
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