Monocyte Chemotactic Protein-1–Interleukin-6–Osteopontin Pathway of Intra-Aneurysmal Tissue Healing

Abstract

Background and Purpose We have previously demonstrated that the local delivery of monocyte chemotactic protein-1 (MCP-1) via a MCP-1-releasing poly(lactic-co-glycolic acid) (PLGA) -coated coil promotes intra-aneurysmal tissue healing. In this study, we demonstrate that interleukin-6 (IL-6) and osteopontin (OPN) are downstream mediators in the MCP-1-mediated aneurysm healing pathway. Methods Murine carotid aneurysms were created in C57BL/6 mice. Drug-releasing coils (MCP-1, IL-6 and OPN) and control PLGA coils were created and then implanted into the aneurysms in order to evaluate their intra-aneurysmal healing capacity. In order to investigate the downstream mediators for aneurysm healing, blocking antibodies for IL-6 receptor and OPN were given to the mice implanted with the MCP-1-releasing coils. A histological analysis of both murine and human aneurysms was utilized to cross-validate the data. Results We observed increased expression of IL-6 in MCP-1-coil treated aneurysms and not in control-PLGA-only treated aneurysms. MCP-1-mediated intra-aneurysmal healing is inhibited in mice given blocking antibody to IL-6 receptor. MCP-1-mediated intra-aneurysmal healing is also inhibited by blocking antibody to OPN. The role of IL-6 in intra-aneurysmal healing is in recruiting of endothelial cells and fibroblasts. Local delivery of OPN to murine carotid aneurysms via OPN-releasing coil significantly promotes intra-aneurysmal healing, but IL-6-releasing coil does not, suggesting that IL-6 cannot promote aneurysm healing independent of MCP-1. In the MCP-1-mediated aneurysm healing, OPN expression is dependent on IL-6; inhibition of IL-6 receptor significantly inhibits OPN expression in MCP-1-mediated aneurysm healing. Conclusions Our findings suggest that IL-6 and OPN are key downstream mediators of MCP-1-mediated intra-aneurysmal healing.

Assessment of Serum Cytokines and Oxidative Stress Markers in Elite Athletes Reveals Unique Profiles Associated With Different Sport Disciplines

“…The heatmap confirms the significant positive correlations between increased power and SOD and MDA, but indicates a negative correlation with pro-inflammatory cytokines MIP-1β, MIG, and VEGF. MIP-1β and MIG represent inflammatory chemokines responsible for recruiting immune cells to damaged tissues, playing a role in the healing process (Wood et al, 2014;Hosaka et al, 2017). The elevated SOD and MDA levels in the high power group confirm previous reports indicating that acute aerobic exercise affects antioxidant levels and redox balance (Kawamura and Muraoka, 2018), which can be detected in the blood as it becomes a source of free radical production in erythrocytes and leukocytes (Nikolaidis and Jamurtas, 2009).…”

Plasma Osteopontin as a Biomarker of Alzheimer’s Disease and Vascular Cognitive Impairment: A Case-Control Study

“…We thus postulated that the atrophy-and CeVD-linked OPN is associated with clinical cognitive performance as well, and our study demonstrated for the first time that increased plasma OPN was associated with poor performance in both global as well as all domain-based cognitive functions, thus expanding upon previous findings of OPN correlations with MMSE [33,34]. The observed associations of OPN with all seven domain-based cognitive functions highlights the potential involvement of OPN, either directly or through regulation of neuroinflammation [27,28], in the pathophysiology of cognitive impairment. This postulate is further supported by the data showing plasma OPN associations with elevation of peripheral inflammatory cytokines including IL-6, IL-8 and TNF.…”

“…OPN, also known as early T-lymphocyte activation (ETA-1) or secreted phosphoprotein 1 (SPP1), is an extracellular phosphoprotein expressed in various tissues and cells in response to stress and injury. It may be upregulated under hypoxic conditions [20,21], atherosclerosis [22,23], angioplasty [24], cerebral ischemia [25,26], and by pro-inflammatory cytokines such as interleukin-1β and interleukin-6 [27,28]. OPN has in turn been shown to regulate macrophage infiltration and cytokine production [29][30][31].…”

The Link between Regional Tidal Stretch and Lung Injury during Mechanical Ventilation

“…Ccl2, or monocyte chemoattractant protein-1 (MCP-1), is responsible for the recruitment of macrophages to the site of inflammation (33,34). The release of IL-6 and Ccl2 are closely linked (35), whereby IL-6 induces Ccl2 expression by peripheral blood mononuclear cells (36) while Ccl2 induces the release of IL-6 by human epithelial cells (37). Increasing levels of IL-6 has been demonstrated in response to injurious ventilation in clinical (20) and experimental (17) studies.…”