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

and HSCs in the inflamed liver, interacts with infiltrating of this condition. Among the various immune cells
monocyte-derived macrophages through the CX3CR1 involved, macrophages have garnered increasing
receptor. This interaction induces macrophage survival attention. Liver macrophages consist of resident KCs and
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and promotes an anti-inflammatory phenotype, thereby infiltrating macrophages derived from monocytes. Hepatic
limiting hepatic inflammation and fibrosis. In addition, macrophages usually maintain a balance between self-
macrophages in inflamed tissue play a crucial role in renewal and differentiation of KCs. However, during acute
phagocytosing cellular debris, which eliminates potential and/or chronic liver injuries, these cells do not significantly
pro-inflammatory signals. This process may, in turn, modify proliferate, and most of the increase in macrophages
the macrophage phenotype, leading to increased MMP comes from monocyte infiltration. Liver macrophages
expression and enhanced ECM degradation. The fibrotic are recognized as key controllers of liver fibrosis, as they
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liver contains a heterogeneous population of macrophages, have the ability to induce fibrosis and inflammation
consisting of both resident KCs and recruited monocytes. through different mechanisms. One example is their
In mice, chronic inflammation leads to a notable increase capacity to secrete TGF-β1, which triggers the activation
in monocytes within the liver, where they differentiate of HSCs and the release of TNF-α, ultimately resulting
into inflammatory macrophages. These liver macrophages in hepatocyte death. Recent research has shown that KCs
are essential in driving fibrosis by stimulating HSCs and do not proliferate during the hepatic fibrosis phase, with
supporting the viability of myofibroblasts. In addition, they the majority of increased liver macrophages originating
play a significant role in the regulation of angiogenesis. The from peripheral monocytes. CCL2, or monocyte
migration of monocytes into the liver relies on chemokine chemoattractant/chemotactic protein-1 (MCP-1), plays
pathways, such as CCL2–CCR2 and CCL1–CCR8, while a crucial role as the primary chemotactic protein for
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their development and survival are aided by CX3CL1– monocytes. Inhibition of CCL2 function is believed to
CX3CR1. 57-62 decrease immune cell attraction to sites of inflammation
and slow down the progression of inflammatory responses.
The process for fibrosis regression is linked to apoptosis Monocytes can be categorized into two subsets: pro-
or inactivation of activated HSCs and myofibroblasts. 63,64 fibrotic classical monocytes and anti-fibrotic non-classical
While increased hepatocyte death contributes to fibrosis monocytes. Classical monocytes, also known as Ly6C
hi
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development, cell death in HSCs plays a crucial role in monocytes, exhibit elevated expression of CCR2 and Ly6C
resolving liver fibrosis. 64-66 After injury repair, infiltrating but reduced levels of CX3CR1. On the other hand, non-
monocytes give rise to Ly6C macrophages, which classical monocytes, known as Ly6C monocytes, have
low
low
are essential for liver fibrosis resolution. 63-66 These high expression of CX3CR1 but lower levels of CCR2 and
macrophages secrete MMPs, such as MMP9, MMP12, Ly6C. Recent studies have shown that the CCR2 expressed
and MMP13, leading to the breakdown of the fibrotic on Ly6C monocytes can bind to MCP-1, whose secretion
hi
scar. Macrophages involved in fibrosis resolution in the is significantly elevated by KC activation. Curcumin
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liver are known as scar-associated macrophages, and they treatment has been shown to reduce the infiltration of
exhibit characteristics that do not fit the conventional M1/ Ly6C monocytes into the liver by decreasing the expression
hi
M2 classification. Furthermore, NK cells play a role in of MCP-1 and CCL7 in patients with liver injury and
inhibiting fibrosis by inducing apoptosis in HSCs through fibrosis. In addition, co-culturing RAW264.7 cells with
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+
the release of IFNγ. CD4 T cells also play a role in the curcumin led to a significant decrease in the expression of
interaction with HSCs and myofibroblasts, with IL-17 MCP-1 and CCL7. Other studies have also reported that
having a direct effect on HSCs through ERK1/2 activation, curcumin possesses anti-fibrotic effects in liver fibrosis
leading to fibrosis and stellate cell activation. Nevertheless, by suppressing the CXCL12/CXCR4 axis and reducing
IL-17 can also counteract fibrosis by promoting the CXCL10 and other pro-inflammatory mediators, thereby
activation of restorative macrophages and the production reducing the severity of the disease by preventing HSC
of matrix-degrading metalloproteinases. Furthermore, activation and migration. 70-72
IL-17 regulates liver regeneration by influencing TGF-β,
IL-4, IL-13, vascular endothelial growth factor, fibroblast 4. The hepatoprotective role of curcumin
growth factor, and TIMP-1. Controlled inflammation and 4.1. Anti-oxidative effects of curcumin
activation at different stages of liver injury are crucial for Several studies have identified and confirmed the
the regulation of fibrosis development.
relationship between curcumin and its associated phenolics
Recent studies on the pathophysiological mechanisms in preventing lipid peroxidation, scavenging free radicals,
of liver fibrosis have shed light on the critical role of and protecting against DNA damage. These compounds are
immune responses in the development and progression believed to function as radical scavengers and antioxidants,

Volume 3 Issue 3 (2024) 9 doi: 10.36922/gpd.3186