HSP70 Modulates the Enhanced Production of Reactive Intermediate Metabolites and a Proinflammatory Cytokine TNF-α Expression in a T Cell Lymphoma

Abstract

Heat shock proteins are intracellular soluble proteins expressed consecutively in all cells. They are immunogenic proteins able to activate antigen-presenting cells by binding through the CD91 receptor and activate both CD4+ and CD8+ T-cells. Macrophage plays a pivotal role in innate immune response and secretes a number of regulatory molecules upon activation. In the present study, we investigate the activation of normal and tumor-associated macrophage to produce the effector molecules which have a role in immunomodulation, especially in the killing of the transformed or tumor cells. In vitro and in vivo treatment of NMO and TAMs (from T-Cell Lymphoma) with optimum dose 10 μg of hsp70 produce effector molecules such as nitric oxide (NO), hydrogen peroxide (H₂O₂) and tumor necrosis factor-α (TNF α). The results of our experiments reveal that the production of effector molecules is dose-dependent, and the result of immunoblots also confirms the increased expression of iNOS. These findings suggest that autologous hsp70 are highly immunogenic and potent activating agents for the enhanced production of effector molecules in NMO and TAMs in a T-cell lymphoma.