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Background: TAM receptors (Tyro3, Axl and Mertk), as subfamily of receptor tyrosine kinases, are intracellular negative feedback regulators and play a crucial role in regulating inflammation and immune response. Aims: To study the expressions and clinical value of TAM receptors in serum and intestinal mucosa of patients with ulcerative colitis (UC). Methods: Forty⁃five patients who were initially diagnosed as active UC from June, 2020 to May, 2021 at the First Affiliated Hospital of Kunming Medical University were enrolled prospectively. Fifteen healthy subjects were served as the control group. Eight cases each in moderate UC group and healthy control group were selected randomly for detection of TAM receptors in serum and intestinal mucosa by ELISA, real⁃time PCR and Western blotting. The correlations of serum Tyro3 with routine clinical indicators of UC were analyzed by Pearson correlation coefficient. Furthermore, immunohistochemistry was used to detect the expression level of TAM receptors in intestinal mucosa in all UC patients and the healthy controls. Results: Expressions of Axl and Mertk were not fully consistent in serum and intestinal mucosa in UC patients. While the serum Tyro3 level, as well as the intestinal Tyro3 mRNA and protein expressions were consistently increased in moderate UC patients than in controls (all P<0.05). Serum level of Tyro3 was positively correlated with platelet count and C⁃reactive protein, and negatively correlated with albumin in moderate UC patients (r=0.97, r=0.96, r=-0.86, all P<0.05). Positivity rate of Tyro3 in intestinal mucosa of UC patients was positively correlated with the disease severity (all P<0.05). Conclusions: Tyro3 is closely related to UC and positively correlated with the disease severity. It might be a promising novel molecular marker and therapeutic target of UC.
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Objective To explore the expression and clinical significance of soluble Axl and Tyro3 receptor tyrosine kinase in systemic lupus erythematosus (SLE).Methods Sandwich enzyme linked immunosorbent assay (ELISA) was used to detect sAxlTK and sTyro3TK in the serum of 140 SLE patients,150 disease controls and 100 healthy controls (HC).The relationships between the serum levels of sAxlTK/sTyro3TK and clinical manifestations,laboratory parameters,disease activity were analyzed in SLE patients.Analysis of variance,Dunnett's t-test,chi-square test and spearman's test were used for statistical analysis.Results The concentrations of sAxlTK [(56±18) ng/ml] and sTyro3TK [(3.9±1.6) ng/ml] were both elevated in serum of SLE patients,which were significantly higher than disease controls [sAxlTK:(41±17) ng/ml;sTyro3TK:(2.6± 1.2) ng/ml] and healthy controls [sAxlTK:(37±10) ng/ml;sTyro3TK:(2.1±0.7) ng/ml].The SLE sAxlTK levels were negatively correlated with lymphocyte count (r=-0.266,P=0.002),hemoglobin (r=-0.480,P＜0.01),platelet count (r=-0.374,P＜0.01),albumin (r=-0.465,P＜0.01),estimated glomerular filtration rate (eGFR,r=-0.230,P=0.006),complement C3 (r=-0.399,P＜0.01) and complement C4 (r=-0.374,P＜0.01).However,the levels of sAxlTK in SLE patients were positively correlated with D-dimer (r=0.371,P＜0.01),creatinine (r=0.278,P＜0.01),24-hour urinary protein quantification (r=0.383,P＜0.01),erythrocyte sedimentation rate (r=0.422,P＜0.01),titre of anti-nuclear antibodies (r=0.271,P=0.002),anti-dsDNA antibody (r=0.299,P＜0.01),anti-nucleosome antibody (r=0.263,P=0.013) and anti-cardiolipin antibody (r=0.309,P＜0.01).In addition,the levels of serum sAxlTK in SLE patients showed positive correlation with the scores of SLEDAI (r=0.307,P＜0.01).Comparisons of sAxlTK levels between patients with high and low disease activity demonstrated a higher level of sAxlTK in the former [(64±17) ng/ml vs (52±16) ng/ml;t=-3.939,P＜0.01].Conclusion The levels of sAxlTK and sTyro3TK are elevated in the serum of SLE patients.The concentration of sAxlTK is correlated with autoantibodies production,hematological and renal involvement in SLE,which may be a serolgical marker for disease activity.
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Lung cancer is still the number one cause of death from cancer worldwide. The clinical effect of platinum-based chemotherapy for non-small cell lung cancer is constrained by the resistance to drug. To overcome chemo-resistance, various modified treatment including combination therapy has been used, but overall survival has not been improved yet. In this study, chemo-resistant lung cancer cells, A549/Cis and H460/Cis, were developed by long-term exposure of cells to cisplatin and the proliferative capability of these resistant cells was verified to be reduced. We found cytotoxic effect of epigallocatechin gallate (EGCG), a major catechin derived from green tea, on both the parental lung cancer cells, A549 and H460, and their cisplatin resistant cells, A549/Cis and H460/Cis. ELISA and Western blot analysis revealed that EGCG was able to increase interlukine-6 (IL-6) production per cell, whereas its downstream effector Signal transducers and activators of transcription 3 (STAT3) phosphorylation was not changed by EGCG, indicating that IL-6/STAT3 axis is not the critical signaling to be inhibited by EGCG. We next found that EGCG suppresses the expression of both Axl and Tyro 3 receptor tyrosine kinases at mRNA and protein level, explaining the cytotoxic effect of EGCG on lung cancer cells, especially, regardless of cisplatin resistance. Taken together, these data suggest that EGCG impedes proliferation of lung cancer cells including their chemo-resistant variants through downregulation of Axl and Tyro 3 expression.