Role of IL-17 Pathways in Immune Privilege: A RNA Deep Sequencing Analysis of the Mice Testis Exposure to Fluoride

Abstract

We sequenced RNA transcripts from the testicles of healthy male mice, divided into a control group with distilled water and two experimental groups with 50 and 100 mg/l NaF in drinking water for 56 days. Bowtie/Tophat were used to align 50-bp paired-end reads into transcripts, Cufflinks to measure the relative abundance of each transcript and IPA to analyze RNA-Sequencing data. In the 100 mg/l NaF-treated group, four pathways related to IL-17, TGF-β and other cellular growth factor pathways were overexpressed. The mRNA expression of IL-17RA, IL-17RC, MAP2K1, MAP2K2, MAP2K3 and MAPKAPK2, monitored by qRT-PCR, increased remarkably in the 100 mg/L NaF group and coincided with the result of RNA-Sequencing. Fluoride exposure could disrupt spermatogenesis and testicles in male mice by influencing many signaling pathways and genes, which work on the immune signal transduction and cellular metabolism. The high expression of the IL-17 signal pathway was a response to the invasion of the testicular immune system due to extracellular fluoride. The PI3-kinase/AKT, MAPKs and the cytokines in TGF-β family were contributed to control the IL-17 pathway activation and maintain the immune privilege and spermatogenesis. All the findings provided new ideas for further molecular researches of fluorosis on the reproduction and immune response mechanism.

IL-17A deficiency alleviate fluoride-induced injury by inhibiting immune response and apoptosis in testis

“…Interestingly, IL-17RC was signi cantly increased in the testis of WT uorosis mice, but the content of IL-17RA was not signi cant and this needs further study. Consistented with previous results, the IL-6, IL-23, IL-1β and TGF-β were increased in the testis when the WT mice exposed 50 mg/L NaF [6]. There have a investigation also indicated that the mRNA levels of TGF-β, IL-1β, IL-6, and IL-21 up-regulated intestis after F exposure [32].…”

“…Research at the cellular level found excessive uoride intake can amplify apoptosis, autophagy and even death of germ cells [5]. Intriguingly, using the sequenced RNA transcripts from the testicles of healthy and uorosis male mice in our study, we found four pathways related to IL-17A signaling that were overexpressed in the testes of uorosis male mice [6]. This indicates that IL-17A may be the pivotal regulator in the process of excessive uoride-induced testicular damage in mice.…”

Attenuation of sleep deprivation dependent deterioration in male fertility parameters by vitamin C

“…The testis is considered as an immune privileged organ, nevertheless, toxic agents and inflammation may overwhelm immune suppressor mechanisms resulting in autoimmune reactions against spermatic antigens. Consequently, this may result in aspermatogenesis and infertility [51]. In the present study, sleep deprivation resulted in significant rise in IL-6 and Il-17, which could be countered by the treatment with vitamin C. Nevertheless, some cytokines such as IL-1, and IL-6 can also produced by Leydig and Sertoli cells [25].…”

“…Excess IL-17 is commonly associated with different types of inflammation, and as for our study, IL-17 serum levels were elevated in the sleep deprived male rats. It has been reported previously that LI-17 and its signaling pathway were highly expressed in mice testis exposed to high fluoride [51]. IL-17 was found to be critically involved in male patients with azoospermic testis with chronic inflammation.…”

Inhibitory effect and mechanism of Tagetes erecta L. fungicide on Fusarium oxysporum f. sp. niveum

“…All unigenes were compared with 4 databases: Nr, COG, KEGG, and Swiss-Prot by BLASTX with cutoff E-value of 10 −5 . Significant differences in gene expression were evaluated using a threshold value of absolute log 2 -fold change >1 with a FDR <0.05 and P < 0.05 39 , 40 . The Pearson’s correlation coefficient between protein and mRNA data was calculated, and scatter plots for FON and FONM expression ratios were created.…”