Mechanisms underlying the production of chemokine CXCL11 in the reaction of renal tubular epithelial cells with CD4+ and CD8+ T cells.

AIM: To study the release mechanism of C-X-C motif chemokine 11 (CXCL11) and other chemokines after the co-cultivation of CD4+ and CD8+ T cells with the renal tubular epithelial cells (RTEC) in the process of allograft renal transplantation rejection. METHODS: The Human CD4+, CD8+ T cells were obtained from the blood of volunteers and kidney transplantation (Ktx) patients, and co-cultured with renal tubular epithelial cells (RTEC) in vitro. RT-PCR was run for detecting the mRNA transcription of CXCL11, IFN-induced protein of 10 (CXCL10), and IL-6 in cells after RTEC was stimulated with IFN-γ or co-cultured with CD4+ and CD8+ T cells. The concentration of CXCL11, CXCL10 and IL-6 in the culture medium was detected by Multiplex Assay after RTEC was stimulated with IFN-γ or co-cultured with CD4+ and CD8+ T cells. IFN-γ receptor antibody was used for interfering with the above reaction and the blocking effect was observed. Western blot was used for protein expression analysis. Finally, we applied renal biopsies from kidney transplantation patients with and without rejection to verify the results of the above experiments by using RT-PCR and Western blot. RESULTS: The mRNA expression of CXCL11 and CXCL10 were significantly increased after RTEC was stimulated with IFN-γ or co-cultured with CD4+ and CD8+ T cells. Multiplex Assay showed that the concentration of CXCL11 and CXCL10 in the supernatant were significantly increased in a time-dependence fashion after stimulation RTEC by IFN-γ. Anti-IFN-γ receptor1 (anti-IFN-γR1) antibody could reduce the production of CXCL11 and CXCL10 in this situation. The concentration of CXCL11 and CXCL11 in the supernatant was significantly increased with a time-dependent effect after the co-culture of CD4+ and CD8+ T cells with RTEC. The anti-IFN-γR1 blocked this effect. Our study showed that the expression levels of CXCL11 and CXCL10 were upgraded in the biopsies of patients with renal transplant rejection comparatively to pre-transplant biopsies, both at mRNA and protein levels. CONCLUSIONS: RTEC and T cells can stimulate each other during the acute rejection of allogeneic kidney transplantation and secret CXCL11，CXCL10 and other chemokines. IFN-γ plays a key role in this process.

Ginkgo biloba extract protects early brain injury after subarachnoid hemorrhage via inhibiting thioredoxin interacting protein/NLRP3 signaling pathway.

OBJECTIVES: To investigate the effect of Ginkgo biloba extract EGb761 in early brain injury (EBI) after subarachnoid hemorrhage (SAH) and its mechanism. MATERIALS AND METHODS: The SAH rat model was constructed and pre-treated with EGb761.The neurological function, severity of SAH, water content of brain tissue, damage degree of the blood-brain barrier, related indexes of oxidative stress, and the level of inflammatory cytokines were compared among the groups. The expression of TXNIP/NLRP3 signaling pathway-related proteins in brain tissues was detected by Western blot. RESULTS: After SAH modeling, the neurological function score was significantly reduced, the degree of brain injury, levels of oxidative stress, inflammatory factors, expression of NLRP3 and TXNIP were all increased. Compared with the SAH rats, the neurological function score of rats pre-treated by EGb761 was higher, the degree of brain injury, levels of oxidative stress and inflammatory factors, expression of NLRP3 and TXNIP were all lower. CONCLUSION: EGb761 could protect neurological injury after SAH and its mechanism may be that EGb761 could inhibit the activation of the TXNIP/NLRP3 signaling pathway and inflammatory reaction after oxidative stress.