AUTHOR=Mándi Yvette , Endrész Valéria , Mosolygó Timea , Burián Katalin , Lantos Ildikó , Fülöp Ferenc , Szatmári István , Lőrinczi Bálint , Balog Attila , Vécsei László 

TITLE=The Opposite Effects of Kynurenic Acid and Different Kynurenic Acid Analogs on Tumor Necrosis Factor-α (TNF-α) Production and Tumor Necrosis Factor-Stimulated Gene-6 (TSG-6) Expression

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01406

DOI=10.3389/fimmu.2019.01406

ISSN=1664-3224

ABSTRACT=<p><bold>Purpose:</bold> The investigation of anti-inflammatory and immunosuppressive functions of Kynurenic acid (KYNA) is now in focus. There is also substantial evidence that TSG-6 has an anti-inflammatory activity. Therefore, in the present study, we compared the effects of newly synthetized KYNA analogs on the TNF-α production in U-937 monocytic cells in correlation with the effects on the TSG-6 expression.</p><p><bold>Methods:</bold> TNF-α production was measured by ELISA, the TSG-6 expression was determined by RTqPCR method. As cytokine inducers <italic>Staphylococcus aureus</italic> and <italic>Chlamydia pneumoniae</italic> were used.</p><p><bold>Results:</bold> KYNA and KYNA analogs attenuated TNF-α production and increased TSG-6 mRNA expression in U-937 cells stimulated by heat inactivated <italic>Staphylococcus aureus</italic>. In contrast, KYNA and some of the KYNA analogs increased the TNF-α production of <italic>C. pneumoniae</italic> infected U-937 cells; however, the newly synthetized analogs (SZR104, SZR 105, and SZR 109) exerted significant inhibitory effects on the TNF-α synthesis. The inhibitory and stimulatory effects correlated inversely with the TSG-6 expression.</p><p><bold>Conclusions:</bold> TSG-6 expression following activation with bacterial components could participate in the suppression of inflammatory cytokines, such as TNF-α, We suppose that the elevation of the TSG-6 expression by KYNA and especially by new KYNA analogs might be one of the mechanisms that are responsible for their suppressive effect on TNF-α production as a feedback mechanism. KYNA and KYNA analogs have an important role in influencing TSG-6 expression, and there is a possible benefit of targeting TSG-6 expression by kynurenines in inflammatory conditions following infections.</p>