Distinct Mechanisms of Inhibition of Interleukin-6-Induced Stat3 Signaling by TGF-β and α-Thrombin in CCL39 Cells

2000 ◽  
Vol 4 (3) ◽  
pp. 151-157 ◽  
Author(s):  
Jagadambika J. Gunaje ◽  
G. Jayarama Bhat
Keyword(s):  
Interleukin 6 ◽  
Stat3 Signaling ◽  
Ccl39 Cells

scholarly journals Interleukin-6/STAT3 Signaling is Prominent and Associated with Reduced Overall Survival in p16 Negative Oropharyngeal Squamous Cell Carcinoma

2018 ◽  
Vol 13 (3) ◽  
pp. 304-312 ◽  
Author(s):  
Gregory B. Lesinski ◽  
Sreenivas Nannapaneni ◽  
Christopher C. Griffith ◽  
Mihir Patel ◽  
Wanqi Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Interleukin 6 ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Stat3 Signaling

scholarly journals Kaposi’s Sarcoma-Associated Herpesvirus Viral Interleukin-6 Signaling Upregulates Integrin β3 Levels and Is Dependent on STAT3

2019 ◽  
Vol 94 (5) ◽  
Author(s):  
Ricardo Rivera-Soto ◽  
Nathan J. Dissinger ◽  
Blossom Damania
Keyword(s):  
Endothelial Cells ◽  
Interleukin 6 ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Αvβ3 Integrin ◽  
Kshv Infection ◽  
Integrin Β3 ◽  
Stat3 Signaling ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of two B-cell lymphoproliferative diseases and Kaposi’s sarcoma, an endothelial-cell-driven cancer. KSHV viral interleukin-6 (vIL-6) is a viral homolog of human IL-6 (hIL-6) that is expressed in KSHV-associated malignancies. Previous studies have shown that the expression of the integrin β3 (ITGB3) subunit is induced upon KSHV infection. Here we report that KSHV vIL-6 is able to induce the expression of ITGB3 and increase surface expression of the αVβ3 integrin heterodimer. We demonstrated using small interfering RNA (siRNA) depletion and inhibitor studies that KSHV vIL-6 can increase ITGB3 by inducing STAT3 signaling. Furthermore, we found that secreted vIL-6 is capable of inducing ITGB3 in endothelial cells in a paracrine manner. Importantly, the ability to induce ITGB3 in endothelial cells seems to be specific to vIL-6, as overexpression of hIL-6 alone did not affect levels of this integrin. Our lab and others have previously shown that vIL-6 can induce angiogenesis, and we investigated whether ITGB3 was involved in this process. We found that siRNA depletion of ITGB3 in vIL-6-expressing endothelial cells resulted in a decrease in adhesion to extracellular matrix proteins. Moreover, depletion of ITGB3 hindered the ability of vIL-6 to promote angiogenesis. In conclusion, we found that vIL-6 can singularly induce ITGB3 and that this induction is dependent on vIL-6 activation of the STAT3 signaling pathway. IMPORTANCE Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of three human malignancies: multicentric Castleman’s disease, primary effusion lymphoma, and Kaposi’s sarcoma. Kaposi’s sarcoma is a highly angiogenic tumor that arises from endothelial cells. It has been previously reported that KSHV infection of endothelial cells leads to an increase of integrin αVβ3, a molecule observed to be involved in the angiogenic process of several malignancies. Our data demonstrate that the KSHV protein viral interleukin-6 (vIL-6) can induce integrin β3 in an intracellular and paracrine manner. Furthermore, we showed that this induction is necessary for vIL-6-mediated cell adhesion and angiogenesis, suggesting a potential role of integrin β3 in KSHV pathogenesis and development of Kaposi’s sarcoma.

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