CCL14

CCL14, also known as HCC-1, is a human plasma chemokine originally collected and purified from the hemofiltrate of patients with chronic renal failure. CCL14 belongs to the small cytokine family of CC chemokines, a cluster of chemokines located on human chromosome 17 that can be expressed in a variety of tissues, including spleen, bone marrow, liver, muscle, and intestine. CCL14 has weak activity against human monocytes and no activity against T lymphocytes, neutrophils, and eosinophils. CCL14 is weakly active against human monocytes and inactive against T lymphocytes, neutrophils, and eosinophils.CCL14 acts as a protein precursor that requires protein hydrolysis to obtain receptor affinity and is processed to yield a mature active protein containing 74 amino acids. The processed HCC-1(9-74) is a chemokine that attracts monocytes, eosinophils and T cells and binds to CCR1, CCR3 and CCR5 chemokine receptors^[2]. Post-translational modifications of CCL14 chemokines, such as N-terminal truncation and glycosylation, also result in differential signaling compared to unmodified ones. For example, both full-length CCL14(1-74) and truncated isoform CCL14(9-74) bind to atypical chemokine receptor 2 (ACKR2), but only truncated CCL14(9-74) shows a propensity for β-restin and induces receptor internalization of ACKR2 compared to CCL14(1-74). Meanwhile, CCL14(1-74) was a weak agonist of chemokine receptor CCR1, but its activity was significantly enhanced after proteolytic cleavage to CCL14(9-74)^[1]. CCL14 has been shown to inhibit HCC cell proliferation by inhibiting cell cycle progression and promoting apoptosis in hepatocellular carcinoma (HCC) cells.CCL14 inhibits HCC tumor growth in nude mice in vivo.CCL14 is also involved in the pathogenesis and progression of various diseases, including allergic airway inflammation and some cancers^[2].