Functional Role of Milk Fat Globule-Epidermal Growth Factor VIII in Macrophage-Mediated Inflammatory Responses and Inflammatory/Autoimmune Diseases

Abstract

Inflammation involves a series of complex biological processes mediated by innate immunity for host defense against pathogen infection. Chronic inflammation is considered to be one of the major causes of serious diseases, including a number of autoimmune/inflammatory diseases, cancers, cardiovascular diseases, and neurological diseases. Milk fat globule-epidermal growth factor 8 (MFG-E8) is a secreted protein found in vertebrates and was initially discovered as a critical component of the milk fat globule. Previously, a number of studies have reported that MFG-E8 contributes to various biological functions including the phagocytic removal of damaged and apoptotic cells from tissues, the induction of VEGF-mediated neovascularization, the maintenance of intestinal epithelial homeostasis, and the promotion of mucosal healing. Recently, emerging studies have reported that MFG-E8 plays a role in inflammatory responses and inflammatory/autoimmune diseases. This review describes the characteristics of MFG-E8-mediated signaling pathways, summarizes recent findings supporting the roles of MFG-E8 in inflammatory responses and inflammatory/autoimmune diseases, and discusses MFG-E8 targeting as a potential therapeutic strategy for the development of anti-inflammatory/autoimmune disease drugs.

Milk fat globule epidermal growth factor 8 inhibits periodontitis in non‐human primates and its gingival crevicular fluid levels can differentiate periodontal health from disease in humans

“…Indeed, in mice, the secreted molecule consists of two N-terminal epidermal growth factor (EGF)-like domains and two Cterminal discoidin-like domains (Stubbs et al 1990). Similar to its mouse counterpart, human MFG-E8 contains two discoidin-like domains; however, it retained only the second EGF-like domain, which includes an integrin-binding RGD motif (Yi 2016).…”

“…). Similar to its mouse counterpart, human MFG‐E8 contains two discoidin‐like domains; however, it retained only the second EGF‐like domain, which includes an integrin‐binding RGD motif (Yi ).…”

“…), whereas it is upregulated in certain other pathological conditions, such as systemic lupus erythematosus, lung fibrosis, melanoma, and breast cancer (Aziz et al. , Yi ). We reasoned that if MFG‐E8 is strongly up‐ or downregulated in human periodontitis (compared to health and/or gingivitis) as reflected by quantitative changes in the GCF, then the monitoring of MFG‐E8 might have predictive or diagnostic value.…”

“…Moreover, we investigated possible association of MFG-E8 GCF levels with human periodontitis. In this context, the expression of MFG-E8 in humans and animal models is strongly regulated in various conditions: It declines considerably in inflammatory conditions, including sepsis, colitis, acute lung injury, ischemia/reperfusion injury, atherosclerosis, and Alzheimer's disease (Ait-Oufella et al 2007, Aziz et al 2011 whereas it is upregulated in certain other pathological conditions, such as systemic lupus erythematosus, lung fibrosis, melanoma, and breast cancer (Aziz et al 2011, Yi 2016. We reasoned that if MFG-E8 is strongly up-or downregulated in human periodontitis (compared to health and/or gingivitis) as reflected by quantitative changes in the GCF, then the monitoring of MFG-E8 might have predictive or diagnostic value.…”

Untitled

“…So we will discuss our results on the basis of anti-inflammatory effect of MFG-E8. MFG-E8 plays role in the phagocytosis of apoptotic cells [16,17]. The serum level of MFG-E8 was found to be higher in SLE patients as compared to very low level in healthy controls [18].…”