Relationships between the activity of MMP1/TIMP1 enzymes and the TH1/TH2 cytokine network.
The evaluation of the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) would appear to be important in cancer patients. Since the activity of these enzymes is regulated at the gene level by cytokines, we studied the serum relationships between MMP1/TIMP1 and the network of TH1/TH2 cytokines in healthy subjects to better understand how the physiological network of cytokines regulates MMP1/TIMP1 activity. Such a study could lead to suggestions for follow-up experiments to create prognostic and diagnostic indices for more efficient disease prevention programs and biotherapeutic treatments of patients. For this purpose, we determined serum levels of MMP1, TIMP1 and interleukin (IL)2, interferon (IFN) gamma, IL4 and IL10 in both healthy men and women (men and women were analyzed separately as hormones are one of the non-cytokine regulatory factors of TH1 or TH2 polarization). These cytokines make up our basic network. Cytokines within the physiological network function simultaneously so mathematical models of multivariate statistical methods were used to study MMP1/TIMP1 and TH1/TH2 network relationships. It has been suggested that mathematical modeling is the only effective way of studying the immune system as a whole. The influence of network activation, antigen presenting cells, antibody response and chemokines on MMP1/TIMP1 balance was also studied. Network activation was evaluated by measuring the levels of soluble IL2 receptors (sIL2R) and sIL6R; the influence of antigen presenting cells was evaluated by measuring serum levels of tumor necrosis factor alpha (TNF alpha) and IL1 beta; antibody response was evaluated by measuring IL5 and IL6 serum levels and the influence of chemokines was evaluated by measuring serum levels of IL8. Our overall results suggest that there are relationships between the activity of MMP1/TIMP1 and the TH1/TH2 network in physiological conditions. These data may be useful in gaining a clearer insight into how the two systems interact and hence regulate the physiological homeostasis. Therefore, this paper provides suggestions for experimental studies on MMP1/TIMp1 enzymes and TH1/TH2 cytokines to create clinical and prognostic markers for patient evaluation.
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Istituto CNR di Tipizzazione Tissutale e Problemi della Dialisi, L'Aquila, Italia. ittppp12@area.ba.cnr.it
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Pellegrini
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D000328:Adult; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000097:blood; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood*; D015375:Receptors, Interleukin-2 / Q000097:blood; D019947:Receptors, Interleukin-6 / Q000097:blood; D012016:Reference Values; D012044:Regression Analysis; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
D016207:Cytokines; D007378:Interleukins; D015375:Receptors, Interleukin-2; D019947:Receptors, Interleukin-6; D019715:Tissue Inhibitor of Metalloproteinase-1; D007371:Interferon-gamma; D020781:Matrix Metalloproteinase 1