Cystitis can be divided into bacterial and non-bacterial cystitis. Bacterial cystitis is more common, also known as urinary tract infection (UTI). Urinary tract infection usually occurs when bacteria from outside the body enter the urethra. and begins to multiply. Uropathogenic Escherichia coli (UPEC) is the most common urinary tract infection pathogen and causes most acute and chronic bacterial urinary tract inflammations. JAK/STAT signaling pathway is used as downstream transduction matters of a variety of cytokines, hormones and growth factors. The JAK/STAT signaling transduction in immune cells regulates the inflammatory responses associated with metabolic abnormalities. Our previous studies proved that the regulation of JAK/STAT signaling significantly affects the infection and inflammation of bladder cells by UPEC. Schistosoma mansoni egg antigen (soluble egg antigen, SEA) contains pro-angiogenic factors that can stimulate the proliferation and migration of endothelial cells, promoting blood vessel proliferation and granuloma formation. Studies have shown that SEA can induce host T cell apoptosis, cause spontaneous immune regulation related to granulomatous inflammation, downregulate Th1 and Th17 responses and reduce related pro-inflammatory cytokines, while promoting Th2 and regulatory B cell responses. Previous studies have also confirmed that SEA can reduce LPS-induced cellular inflammation and is related to the JAK/STAT signaling pathway.

This study evaluated the effects of SEA on bladder UPEC infection, and observed their regulations on JAK/STAT pathway and related inflammatory factors. The number of colonies were evaluated by plate coating, fluorescent microscopy, and flow cytometry. qPCR and Western blot analyses were also performed to investigate the mechanism underlying SEA-mediated inhibition.

Our data showed that SEA can effectively inhibit the colony formation of UPEC. The results of plate coating, fluorescent microscopy, and flow cytometry all clearly showed a significant reduction in the number of colonies. In addition, qPCR and Western blot analysis also confirmed that SEA inhibit the activity and growth of UPEC in bladder cells through the JAK/STAT pathway, especially STAT1, which plays a very important role in this pathway. We have previously used other types of drugs to test bladder infections. The peptides RNase 7 and LCN2, and the resveratrol-related pterostilbene also have very good antibacterial effects. It was proved that these three are the same as the SEA, affecting bladder cells through the JAK/STAT pathway; and also showed that the JAK/STAT pathway is an important pathway in infection-related cell models. More experiments and analyses should be conducted on its upstream and downstream related pathways in the future.

Our results may be helpful for the prevention and treatment of clinical cystitis, and provide a new treatment direction for cystitis and reduce recurrence