Induction of IL-6 and IL-8 by activation of thermosensitive TRP channels in human PDL cells

Objective: The oral cavity is often exposed to not only diverse external pathogens but also dramatic temperature changes. In this study, we investigated the effect of thermal stress on PDL cells with a focus on the inflammatory responses and bone homeostasis. Design: The PDL cells were isolated from healthy premolar extracted for orthodontic reasons, and examined using intracellular calcium concentration ([Ca²⁺]_i) measurement and reverse transcription-polymerase chain reaction for pro-inflammatory cytokines and bone remodelling mediators. Results: We detected the expression of thermosensitive transient receptor potential (TRP) channels, such as TRPV1, TRPV2, TRPV3, TRPM8, and TRPA1. Functional activation of the channels by thermal stress and their specific agonists increased [Ca²⁺]_i and interleukin (IL)-6 and IL-8 mRNA expression. A selective Ca²⁺ chelator, BAPTA-AM, prevented TRP channel agonists-mediated IL-6 and IL-8 induction. Unlike pro-inflammatory cytokines, the expression of bone remodelling mediators, including receptor activator of nuclear factor-kappa B ligand and osteoprotegerin, was not altered by treatment with TRP channel agonists. Conclusions: The activation of thermosensitive TRP channels induced IL-6 and IL-8 expression by increasing [Ca²⁺]_i in human PDL cells. Therefore, thermal stress may play a critical role in the inflammatory responses of PDL cells.