The Role of JAK2/STAT3 Signaling Pathway Regulation in Macrophage Apoptosis During Brucella M5-90 Infection

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.

Brucella M5-90 Enfeksiyonu Süresince Makrofaj Apoptozisinde JAK2/STAT3 Uyarı Yolağının Rolü

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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Kafkas Üniversitesi Veteriner Fakültesi Dergisi-Cover
  • ISSN: 1300-6045
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 1995
  • Yayıncı: Kafkas Üniv. Veteriner Fak.
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