IL-12-mediated transcriptional regulation of matrix metalloproteinases

Matrix metalloproteinases (MMPs) are extracellular matrix (ECM) remodelling enzymes involved in developmental processes, tissue remodelling and repair, inflammatory and immune diseases and cancer. In a recent issue of Bioscience Reports (vol. 37, issue 6, BSR20170973), Liu and colleagues investigated the expression of MMPs such as MMP-1 (interstitial collagenase), MMP-3 (stromelysin 1) and MMP-13 (collagenase 3) in human periodontal ligament fibroblasts (hPDLFs) regulated by interleukin-12 (IL-12), a cytokine implicated in inflammatory and immune responses. They showed that IL-12 activates canonical nuclear factor-κB (NF-κB) signalling leading to increased expression of MMP-1, MMP-3 and MMP-13, and to a smaller reduction in the expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) at both mRNA and protein levels, with corresponding changes in the secreted levels of these ECM-remodelling and immune regulatory metalloproteinases. While canonical NF-κB signalling regulates these MMPs, it also interacts with additional factors to determine whether some of these MMPs are induced or downregulated, in response to IL-12. Here, we comment on the possible mechanisms of IL-12-mediated transcriptional regulation of MMPs.

Interstitial collagenase and their endogenous regulators in squamous cell cervical carcinoma

Interstitial collagenase (MMP-1) belongs to the family of matrix metalloproteinases (MMP), which play a key role in generalization processes of invasion and metastasis, which determine the degree of tumor malignancy. MMP-1 refers to secreted, inducible MMP, the expression of which in normal tissues is not defined. Induction of expression of MMP in CSS in the tumor occurs under the action of oncogenes of HPV, and in areas adjacent to the tumor normal tissue under the action of the inductor expression of MMP – EMMPRIN (CD147), which expressively on the surface of tumor cells. The aim of this study is to determine the possibility of expression ofMMP-1 and its regulators (tissue inhibitors TIMP-1 and activator - plasminogen activator – ADF) in morphologically normal body of the uterus during CSS. The study was carried out using on a tissue “tape” – postoperative specimens of the uterus when the diagnosis of CSS. All of the samples was expressed HPV16 gene E7. It was shown that: 1. The increase of MMP-1 expression, low expression (or lack thereof) of its inhibitors TIMP-1 and a very clear expression of the activator take place in the tumor when CSS that lead to increased activity of MMP-1, and aims to increase the destructive (invasive) potential of the tumor. 2. In morphologically normal tissue of the uterus during CSS the expression of MMP-1 can occur from the vaginal wall to the bottom of the uterine cavity, but at a much lower level than in the tumor. 3. These data indicate the possibility of development of a destructive process in morphologically normalnyh body tissues of the uterus during CSS, important for understanding the mechanism of tumor progression, and suggest participation in the process of expression of MMP-1 signaling by the type of epithelial-mesenchymal interaction .