Possible association of decreased serum CXCL14 levels with digital ulcers in patients with systemic sclerosis

Abstract

CXCL14 serves as a chemoattractant for activated macrophages, immature dendritic cells and natural killer cells, as well as an antiangiogenic factor by preventing the migration of endothelial cells. CXCL14 also exerts an inhibitory effect on the CXCL12/CXCR4 signaling pathway, which is involved in the maintenance of T‐helper (Th)2 bias, and promotes Th1 immune response under the physiological and pathological conditions. Because CXCL14‐mediated biological processes seem to be involved in the development of systemic sclerosis (SSc), which is characterized by Th2/Th17‐skewed immune polarization and impaired neovascularization, we investigated the clinical correlation of serum CXCL14 levels in patients with this disease. Serum CXCL14 levels were significantly decreased in SSc patients compared with healthy individuals and in diffuse cutaneous SSc patients relative to limited cutaneous SSc patients. SSc patients with digital ulcers had serum CXCL14 levels significantly lower than those without. Furthermore, i.v. cyclophosphamide pulse significantly increased serum CXCL14 levels as compared with the baseline in SSc patients with interstitial lung disease successfully treated with this therapy. These results indicate that decreased CXCL14 expression may contribute to the maintenance of Th2‐skewed immune polarization and dysregulated neovascularization, both of which underlie the developmental process of SSc.

Endothelial CCR6 expression due to FLI1 deficiency contributes to vasculopathy associated with systemic sclerosis

“…For instance, CXC chemokines with glutamic acid-leucine-arginine (ELR) motif in their N terminus are potent promoters of angiogenesis, while those without ELR motif are potent inhibitors of angiogenesis [ 46 ]. Of note, the various CXC chemokines, such as CXCL4 (ELR-) [ 47 ], CXCL5 (ELR+) [ 26 ], CXCL6 (ELR+) [ 27 ], CXCL12 (ELR−) [ 48 ], CXCL13 (ELR−) [ 24 ], and CXCL14 (ELR−) [ 49 ], are thought to be associated with the development of SSc vasculopathy. With respect to CC chemokines, the broad-spectrum inhibitor of CC chemokines, 35 K, suppresses inflammation-driven angiogenesis, whereas preserving physiological ischemia-mediated angiogenesis [ 50 ].…”

Endothelial CCR6 Expression Due to FLI1 Deficiency Contributes to Vasculopathy Associated with Systemic Sclerosis

“…For instance, CXC chemokines with glutamic acidleucine-arginine (ELR) motif in their N terminus are potent promoters of angiogenesis, while those without ELR motif are potent inhibitors of angiogenesis [41]. Of note, the various CXC chemokines, such as CXCL4 (ELR-) [42], CXCL5 (ELR+) [30], CXCL6 (ELR+) [31], CXCL12 (ELR-) [43], CXCL13 (ELR-) [24], and CXCL14 (ELR-) [44], are thought to be associated with the development of SSc vasculopathy. With respect to CC chemokines, the broad-spectrum inhibitor of CC chemokines, 35K, suppresses in ammation-driven angiogenesis, whereas preserving physiological ischemia-mediated angiogenesis [45].…”

Serum C‐X‐C motif chemokine ligand 14 levels are associated with serum C‐peptide and fatty liver index in type 2 diabetes mellitus patients

“…For instance, several human studies have presented serum CXCL14 levels to be significantly elevated in individuals with idiopathic pulmonary fibrosis 21 and acute liver injuries of various etiologies 22,23 . In contrast, a decrease in the serum CXCL14 level is linked to the stage advancement of chronic HBV infection 24 and the severity of systemic sclerosis 25 . In addition, the association between CXCL14 and oncogenesis has attracted the attention of researchers 9 .…”