Cell biology international
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Toll-like receptor 4 (TLR4) is involved in multiple malignancies; however, the role of TLR4 in the pathogenesis of malignant pleural effusion (MPE) remains unknown. The objectives of this study were to explore the impact of TLR4 signaling on the development of MPE in a murine model and to define the underline mechanisms by which TLR works. Development of MPE as well as proliferation and angiogenesis of pleural tumor were determined in TLR4(-/-) and wild type mice. ⋯ TLR4 deficiency promoted MPE formation and, thus, accelerated the death of mice bearing MPE, whereas intraperitoneal injection of anti-IFN-γ mAb or recombinant mouse IL-17 protein into TLR4(-/-) mice was associated with improved survival. Our data provides the first definitive evidence of a role for TLR4 signaling in protective immunity in the development of MPE. Our findings also demonstrate that TLR4 deficiency promotes MPE formation and accelerates mouse death by enhancing Th1 and suppressing Th17 response.