ABSTRACT
Fibrosis is the common pathological basis of various lesions. It is mainly manifested as excess collagen deposition and fibrous connective tissue in tissues with destructed structures and impaired function. At present, the pathogenesis of fibrosis is still unclear, and no effective treatment or prevention for fibrosis is available. In recent years, numerous studies have shown that chemokine CXCL16 and its receptor CXCR6 play an important role in the development of fibrosis. This paper summarizes the biological character-istics of CXCL16/CXCR6 axis and its role in fibrosis.
ABSTRACT
Objective:It has been found that serum CXCL16 concentration in rheumatoid arthritis (RA) patients are significantly higher than those in osteoarthritis (OA) and normal subjects, and are positively correlated with disease activity and bone erosion.However, how is CXCL16 involved in the pathogenesis of RA is unclear.To evaluate the expression of CXCL16 and its receptor CXCR6 in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients, and to explore the role of CXCL16 in the proliferation of RA-FLS.Methods: FLS were isolated from knee synovial tissues obtained from 8 patients of RA, 7 osteoarthritis (OA) and 3 normal controls.The diagnosis of RA was in line with the 1987 American Rheumatology Association (ACR) RA classification criteria, osteoarthritis met the 1996 ACR revised knee osteoarthritis classification criteria.Control synovium were obtained from trauma caused knee joint injury in healthy individuals who required surgery.Human knee FLS were cultured by tissue explants adherent method.FLS between passages 3 and 5 were used in the experiment.Expression of CXCL16 and its receptor CXCR6 were performed in Western blot analysis.FLS proliferation follo-wing stimulation with TNF-α and different concentrations of CXCL16 was examined by cell counting kit-8 (CCK-8).Expression of phosphorylated AKT (pAKT) in RA-FLS stimulated by CXCL16 was quantified by Western blot.Different concentrations of recombinant human CXCL16 were added to the culture medium of RA-FLS.After 48 h culture, supernantants were collected, and TNF-α, IL-6, RANKL and MMP3 in culture supernatants of RA-FLS were determined by enzyme-linked immunosorbent assays (ELISA) operated following the kit instructions.Results: Expression of CXCL16 and CXCR6 in RA-FLS was significantly higher than that of OA and controls (P<0.05), but no significant difference was found between OA-FLS and control FLS.Proliferation of RA-FLS was markedly up-regulated after stimulation of CXCL16 (P <0.05).In the case of the CXCL16 stimulated OA-FLS and control FLS, the FLS proliferation remained basically unchanged.Expression of phosphorylated AKT in RA-FLS increased remarkably in condition of CXCL16 (50,100, 200 μg/L) stimulation.The levels of IL-6 and RANKL in culture supernatants of RA-FLS were obviously increased under CXCL16 (200 μg/L) stimulation, while TNF-α and MMP-3 levels in the culture supernatants remained unchanged after CXCL16 (200 μg/L) stimulation.Conclusion: This study shows that the expression of CXCL16 and its receptor was highly elevated in RA-FLS.Recombinant CXCL16 promoted RA-FLS proliferation and activation in vitro.All these indicate that CXCL16 play an important role in the pathogenesis of RA, anti-CXCL16 treatment may help to relieve inflammation and bone damage of RA patients.However, due to the limitations of this study, the role of CXCL16 and its receptors in RA-FLS remains to be elucidated by further research.
ABSTRACT
ObjectiveTo explore the role of CXCL16/CXCR6 axis on the metastasis of human lung cancer.MethodsImmunohistochemistry and immunocytochemistry analysis were performed to detect the expression of CXCL16/CXCR6 in human lung cancer samples as well as A549,95D and H292 cell lines,respectively.The effects of CXCL16 on the viability and invasiveness of the three lung cancer cell lines were examined by MTT and in vitro invasion assay,respectively.ResultsHuman native lung cancer cells co-expressed CXCR6 and CXCL16 protein.Compared to the normal lung tissues,there was a stronger specific staining for both CXC16 and CXCR6 protein in the lung cancer tissues.Three kinds of lung cancer cell lines,including A549,95D and H292,all expressed CXCL16 and CXCR6 protein.Furthermore,human recombinant CXCL16 significantly promoted the viability and invasiveness of A549,95D and H292 cells.The stimulated action of CXCL16 on lung cancer cell lines could be effectively blocked by CXCL16 neutralizing antibody.Conclusion CXCL16 and CXCR6 protein are co-expressed in human native lung cancer.CXCL16 is able to promote the viability and invasiveness of lung cancer cell lines,which might be the molecular mechanisms on the metastasis of lung cancer.