CXCL10

1. 본문

CXCL10 (C-X-C Motif Chemokine Ligand 10) is a small cytokine belonging to the CXC chemokine family. It is also known as Interferon gamma-induced protein 10 (IP-10) or small-inducible cytokine B10. Here's a breakdown of its key characteristics and functions:
Structure and Genetics:

• Gene: The CXCL10 gene is located on chromosome 4 in humans and contains four exons and three introns.
• Protein: The gene encodes a protein of 98 amino acids, with a molecular weight of approximately 8.7 kDa (though other sources mention 10 kDa and 12 kDa).
• Homologs: Rat and mouse homologs of human CXCL10 are mob-1 and crg-2, sharing 70% and 78% amino acid homology, respectively.

Function:

• Chemotaxis: CXCL10 is a chemoattractant, meaning it attracts specific cells. It primarily recruits and activates leukocytes like T cells, eosinophils, monocytes, and NK cells.
• Immune Response: It plays a crucial role in mediating immune responses by activating and recruiting leukocytes to sites of inflammation or infection. It is considered a pro-inflammatory cytokine.
• CXCR3 Binding: CXCL10 exerts its effects by binding to the CXCR3 receptor, particularly the CXCR3A isoform. CXCL9 and CXCL11 also bind to this receptor.
• Signal Transduction: Binding of CXCL10 to CXCR3 activates G protein-mediated signaling, leading to:
• Activation of phospholipase C-dependent pathway.
• Increased intracellular calcium production.
• Actin reorganization.
• Angiostatic Effects: CXCL10 can inhibit the formation of new blood vessels (angiogenesis). It achieves this by binding to the CXCR3B receptor subunit, inhibiting endothelial cell proliferation, and inducing apoptosis. It can also antagonize pro-angiogenic factors like bFGF and VEGF.
• Apoptosis, Cell Growth and Differentiation: CXCL10 is involved in the induction of apoptosis (programmed cell death) and regulation of cell growth, playing a crucial role during viral infection.
• Role in the Central Nervous System: Plays a part in neuronal reorganization after brain injury. It activates microglia (the brain's resident macrophages) and guides to lesion site.

Regulation:

• Induction: CXCL10 expression is induced by interferon-gamma (IFN-γ) and other stimuli, including:
• Type-1 and type-2 interferons
• Inflammatory stimuli like TNFα
• Lipopolysaccharides (LPS)
• Regulation Sites: The region upstream from CXCL10's transcriptional start site contains regulatory elements, including binding sites for:
• Nuclear factor-κB (NF-κB)
• Activator protein 1 (AP-1)
• Interferon-stimulated response element (ISRE)
• Heat shock (HS) factors

Cellular Sources:CXCL10 is produced by various cell types, such as:

• Monocytes
• Neutrophils
• Endothelial cells
• Keratinocytes
• Fibroblasts
• Mesenchymal cells
• Dendritic cells
• Hepatocytes
• Astrocytes
• T cells
• Epithelial cells
• Thyroid cells

Clinical Significance:

• Biomarker: CXCL10 can serve as a biomarker of T cell activity.
• Disease Association: Elevated CXCL10 levels are associated with various diseases, including:
• Multiple sclerosis (MS)
• Infectious diseases
• Cancer
• Spotted Fever
• Cryptosporidiosis

Because of its involvement in various diseases, CXCL10 is being investigated for potential therapeutic implications.