Cellular and Molecular Effects of High-Molecular-Weight Heparin on Matrix Metalloproteinase 9 Expression

Abstract

Blood sampling with different anticoagulants alters matrix metalloproteinase (MMP-) 9 expression, thus influencing its concentration and diagnostic validity. Here, we aimed to evaluate the effects of different anticoagulants on MMP-9 regulation. MMP-9 expression was assessed in response to ethylenediaminetetraacetic acid, citrate, and high-/low-molecular-weight heparin (HMWH, LMWH) in co-culture experiments using THP-1, Jurkat, and HT cells (representing monocytes, T, and B cells). Triple and double cell line co-culture experiments revealed that HMWH treatment of THP-1 and Jurkat led to a significant MMP-9 induction, whereas other anticoagulants and cell type combinations had no effect. Supernatant of HMWH-treated Jurkat cells also induced MMP-9 in THP-1 suggesting monocytes as MMP-9 producers. HMWH-induced cytokine/chemokine secretion was assessed in co-culture supernatant, and the influence of cytokines/chemokines on MMP-9 production was analyzed. These experiments revealed that Jurkat-derived IL-16 and soluble intercellular adhesion molecule (sICAM-) 1 are able to induce MMP-9 and IL-8 production by THP-1. As a consequence, the increased MMP-9 expression found in HMWH blood samples may be influenced by HMWH-dependent secretion of IL-16 and sICAM-1 by T cells resulting in an increased production of MMP-9 and IL-8 by monocytes. IL-8, in turn, may support MMP-9 and its own expression in a positive autocrine feedback loop.

Mechanism of azithromycin in airway diseases

“…3 The abnormal expression of IL-8 in tumor cells affects metastatic potential through the production and secretion of matrix metalloproteinase 9 (MMP9). 4 AZM may suppress the activity and production of MMP9 in airway epithelial cells, inhibiting airway mucus hypersecretion. Moreover, AZM can inhibit IL-8 production induced by tumor necrosis factor (TNF)-a.…”

Matrix Metalloproteinases: How Much Can They Do?

“…T cells secrete the mediators IL-16 and sICAM-1, which induce monocytic IL-8 production. Together, these factors induce continuous IL-8 secretion as well as enhanced MMP-9 production by monocytes[22].…”

“…The content of this Special Issue highlights the multiple biological functions of these proteolytic enzymes and includes four review articles [4,[15][16][17] and 10 original articles [18][19][20][21][22][23][24][25][26][27]. The articles address the role of MMPs, ADAMs, and ADAMTSs, in normal physiology as well as in neoplastic and tissue destructive processes.…”

“…TNF-α increased cancer cell invasion of the mesothelium via a process that was inhibited by MMP-9 gene silencing but not by MMP-2 gene silencing and was rescued by the addition of MMP-9 ( Figure 1). Huber et al [22] set out to elucidate the cellular mechanisms involved in the differential effect of high-molecular-weight heparin (HMWH) compared with that of other anticoagulants on MMP-9 blood levels. For this purpose, monocytic and T and B lymphocytic cell lines were cocultured.…”

“…The researchers demonstrated that HMWH increased IL-16 and sICAM-1 secretion by T lymphocytes, which in turn increased IL-8 and MMP-9 production by monocytes ( Figure 2). Huber et al [22] set out to elucidate the cellular mechanisms involved in the differential effect of high-molecular-weight heparin (HMWH) compared with that of other anticoagulants on MMP-9 blood levels. For this purpose, monocytic and T and B lymphocytic cell lines were cocultured.…”