Brucellosis is serious zoonotic disease affecting both animals and humans. Brucella inhibits the apoptosis of host macrophages. And the JAK2/STAT3 pathway regulates various cellular physiological activities. However, the association between Brucella-mediated inhibition of macrophage apoptosis and regulation of the JAK2/STAT3 pathway is unclear. In the current study, We tested the the activation of JAK2/ STAT3 pathway and evaluated its function during Brucella M5-90 infection in cells. The result was found that infection with Brucella M5-90 activated the JAK2/STAT3 pathway and induced phosphorylation of both JAK2 and STAT3 in a time-dependent manner. JAK2 and STAT3 phosphorylation were inhibited by AG490 in a dose-dependent manner. Inhibition of the JAK2/STAT3 pathway with AG490 significantly induced proinflammatory responses, macrophage apoptosis at the transcriptional and protein levels, as well as intracellular survival and replication of Brucella M5-90. This study indicates that the JAK2/STAT3 pathway plays a major role in macrophage apoptosis induced by infection with Brucella M5-90. In addition, TNF-α plays a major role in the regulation of the JAK2/STAT6 pathway during Brucella M5-90 infection. The above information may help to unravel the pathogenic mechanism of Brucella infection.
Brusellozis hem hayvanları hem de insanları etkileyen ciddi zoonotik bir hastalıktır. Brucella konakçı makrofajlarının apoptozisini inhibe eder. JAK2/STAT3 yolağı çeşitli hücresel fizyolojik aktiviteleri düzenler. Ancak Brucella aracılı makrofaj apoptozisinin inhibisyonu ile JAK2/STAT3 yolağının düzenlenmesi arasındaki ilişki belirsizdir. Bu çalışmada; JAK2/STAT3 yolağının aktivasyonu çalışılarak hücrelerde Brucella M5-90 enfeksiyonu boyunca fonksiyonu değerlendirildi. Brucella M5-90 ile enfeksiyonun JAK2/STAT3 yolağını active ettiği ve hem JAK2 hem de STAT3 fosforilasyonunu zamana bağlı olarak uyardığı tespit edildi. JAK2 ve STAT3 fosforilasyonu doza bağlı olarak AG490 ile inhibe edildi. JAK2/STAT3 yolağının AG490 ile inhibe edilmesi anlamlı derecede proinflamatory yanıtı, transkripsiyon ve protein seviyesinde makrofaj apoptozisini ve Brucella M5-90’nın hücre içi hayatta kalma ve replikasyonunu uyardı. Bu çalışma Brucella M5-90 enfeksiyonu ile oluşturulan makrofaj apoptozisinde JAK2/STAT3 yolağının önemli bir rol oynadığını göstermiştir. Ayrıca, Brucella M5-90 enfeksiyonu süresince JAK2/ STAT6 yolağının regülasyonunda TNF-α önemli rol oynar. Yukarıda ifade edilen bulgular Brucella enfeksiyonunun patogenezini açığa çıkarmada faydalı olabilir..
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