RvD1 Promotes Tight Junction Integrity in Irradiated Salivary Gland Epithelium

Objectives: Head and neck cancer radiotherapy (RT) regularly destroys the salivary glands (SG), leading to a loss of secretory function (i.e., hyposalivation). Although the mechanisms underlying the loss of SG function after RT are not clearly understood, previous studies reported that the damage of tight junctions (TJ) is commonly seen, which has a negative impact on polarized saliva secretion. In light of the high degree of need and the limitations of current therapies, development of alternative treatments to restore SG functioning is essential. For this purpose, restoring TJ integrity in irradiated SG epithelium could be a potential target to restore saliva secretion. Particularly, our group has shown that specialized lipid mediators, such as resolvin D1 (RvD1), promotes TJ integrity and enhances saliva flow rates in a Sjögren's syndrome-like model. However, the use of RvD1 to manage RT damage was never conducted in SG, thereby adding novelty to this approach. Therefore, the goal of this study was to determine whether RvD1 promotes TJ integrity after different RT regimens.
Methods: We exposed salivary cells (e.g., rat parotid Par-C10 cells) to single and fractionated radiation doses in vitro. Next, cells were cultured and treated with RvD1 (100 ng/ml) after each radiation dose. Then, cell polarity and barrier function were studied at different time points.
Results: SG epithelium treated with RvD1 maintained TJ organization and barrier function as compared to non-irradiated epithelium, whereas irradiation without RvD1 treatment caused TJ disruption and decreased barrier function.
Conclusions: The use of RvD1 along with distinct RT regimens restored TJ structure and function in irradiated SG epithelium. Together, these results warrant additional studies using RvD1 as a novel approach to in vivo head and neck irradiated mouse models using either single or fractionated doses.