| Monocyte chemotactic protein-1 (MCP1) |
Increased expression by stromal and immune cells triggered via NF-κB-mediated response to pathogen-associated and molecular-associated molecular patterns released by damaged cells. Promotes upregulation of chemokine receptor expression and infiltration of immune cells to tissues. Acts as a key cytokine in age-related senescence-associated secretory phenotype (SASP), and contributes to ‘inflammaging’ by propagation of pro-senescent signals through the tissue and promotion of chronic inflammation associated with chronic disease.
|
[14,15,16,17,18] |
| Macrophage migration inhibitory factor (MIF) |
Fundamental to the pro-inflammatory response being released by immune cells in response to pathogen-associated molecular patterns. Propagates inflammatory response by autocrine and paracrine stimulation of pro-inflammatory cytokine release. Elevated expression in sepsis correlating with cortisol and IL6 expression and prognosis of disease progression. Upregulated in acute respiratory distress syndrome where it is directly linked to promotion of the inflammatory response and production of pro-inflammatory cytokines.
|
[19,20,21,22,23,24,25,26,27,28,29] |
| Basic fibroblast growth factor-2 (FGF2) |
Regulator of cellular activity during tissue repair and regeneration, including mediation of inflammatory response during the acute phase of injury. Promotes upregulation of pro-inflammatory cytokines in immune cells and tissue-resident somatic cells. Increased expression associated with inflammation results in tissue fibrosis, contributing to inflammaging and impairment of tissue function that manifests as age-related chronic diseases and disorders.
|
[30,31] |
| Vascular endothelial growth factor (VEGF) |
Increased expression during inflammatory response to promote angiogenesis and support the infiltration of immune cells. Contributes to the regulation of adhesion molecule expression to control the infiltration of immune cells across capillaries. Increased levels work with HIF1α, angiopoietins, TNFα, and IL8 to promote angiogenesis. Angiogenesis and microvesicle remodelling are a hallmark of inflammatory associated diseases, including psoriasis, RA, inflammatory bowel disease, and diabetic retinopathy.
|
[32,33,34,35,36] |
| Hepatocyte growth factor (HGF) |
Expressed in immune cell organs, including bone marrow, thymus, tonsils, and spleen with a key role in supporting haematopoiesis and immune cell development. Elevated expression during regeneration of tissues in response to a pro-inflammatory environment and particularly cytokines IL1α, IL1β, TNF, and interferon (IFN)-γ. Dysregulation of HGF activity is implicated in inflammatory disorders through overstimulation of T-cells and production of pro-inflammatory cytokines, maturation of monocytes to macrophages, and migration of dendritic cells.
|
[37,38,39,40,41,42,43,44,45,46] |
| Insulin-like growth factor-1 (IGF1) |
Anti-inflammatory cytokine widely expressed by immune cells. Regulates macrophage polarisation from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. Shift from M1 to M2 macrophage polarisation is proposed as being protective against autoimmune and autoinflammatory disorders but its overexpression may be explicit in the progression of fibrosis.
|
[47,48,49,50] |
| Platelet-derived growth factor (PDGF) |
Expressed by monocytes and platelets with increased expression in response to injury where it moderates immune cell activity, including inhibiting dendritic cell cytotoxic activity, and modulation of macrophage and lymphocyte activity. Reduced PDGF levels during the early inflammatory phase of arthrosclerosis result in increased monocyte and pro-inflammatory T-cell presence within developing lesions.
|
[51,52,53,54,55] |
| Transforming growth factor-β1 (TGFβ1) |
Key growth factor in the maintenance of immune cell homeostasis. Stimulates pathogenic Th17 cell differentiation in combination with IL6, IL1, and IL23 and is a potent mediator of autoimmune disorders.
|
[56,57] |
| Stromal cell-derived factor-1/C-X-C motif chemokine-12 (SDF-1α/CXCL12/) |
Regulates immune cell trafficking with dysfunction causing pathological recruitment and retention of immune cells to tissues and progression of autoimmune and autoinflammatory disorders. Contributes to the chronic inflammation of inflamed joints in RA disease by promotion of activated immune cell homing and retention within the joint. Directly promotes joint tissue erosion by promoting migration and maturation of osteoclasts, inducing chondrocyte necrosis and promotion of neovascularisation. Elevated expression in inflammatory psoriasis with contribution to promotion of angiogenesis in skin lesions. Elevated expression in cerebral spinal fluid, astrocytes, and monocytes/macrophages of active lesions in patients with multiple sclerosis.
|
[58,59,60,61,62,63,64,65,66] |
