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Gene & Protein in Disease Modulating immune response in liver by curcumin

Figure 2. The Immunological mechanisms operating in development of liver fibrosis

ligand (CCL) 2, and CCL5, leading to HSC activation and and IL-13. Local macrophages can adopt a wound-healing
the influx of additional immune cells, such as monocyte- phenotype, producing mediators, such as MMP9, MMP12,
derived macrophages, into the vicinity. 49-53 The regulation and MMP1, which assist in breaking down the ECM and
of infiltrating monocytes is predominantly governed by resolving fibrosis. 54-56 In cases of chronic liver injury, levels
the C–C motif chemokine receptor (CCR) 2 and its ligand of inflammation-promoting mediators increase, facilitating
CCL2, which plays significant roles in the progression of leukocyte migration to injury sites through complex
fibrosis. The primary cause of hepatic inflammation is the interactions with endothelial cells and ECM components.
recruitment of pro-inflammatory cells. Chemoattractant molecules guide lymphocytes through
The interaction between inflammatory cells and HSCs the endothelium, with C-X-C chemokine receptor
intensifies and perpetuates the pro-fibrogenic state in (CXCR) 3 activation by ligands, such as C-X-C chemokine
the liver. Activated HSCs influence the recruitment ligand (CXCL) 9, CXCL10, and CXCL11 aiding their
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of immune cells by releasing pro-inflammatory and migration. Myofibroblasts also release cytokines, such as
chemoattractant molecules. In addition, they secrete IL-6, hepatocyte growth factor, and TGF-β, to encourage
ECM, forming a network that facilitates the migration and lymphocyte movement. The development of fibrosis is
+
retention of leukocytes. Activated macrophages, on the dependent on CD4 T cell responses, with Th2-polarized
other hand, release cytokines that further stimulate HSCs. T cells promoting the expression of pro-fibrogenic genes
In response, HSCs produce cytokines such as macrophage in myofibroblasts and the synthesis of immunoregulatory
colony-stimulating factor and IL6, which enhance the mediators in macrophages. Th2-polarized T cells play a
pro-fibrotic activity of macrophages. Furthermore, the critical role in fibrosis progression by influencing cellular
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activation of KCs increases nuclear factor kappa B (NF- characteristics and cytokine production.
κB) activation in HSCs, thereby promoting the release The reduction of pro-inflammatory and pro-fibrotic
of pro-inflammatory cytokines. 55,56 Macrophages exhibit signals expressed by macrophages during fibrogenesis can
varying phenotypes throughout the progression of potentially change the local environment, favoring fibrosis
injury, eventually shifting toward an anti-inflammatory resolution. A significant study by Tacke and colleagues
response characterized by cytokines such as IL-10, IL-4, demonstrated that CX3CL1, produced by hepatocytes

Volume 3 Issue 3 (2024) 8 doi: 10.36922/gpd.3186