Salivary Epithelial Cells Express Functional Resolvins Receptors

Our understanding of the endogenous mechanisms that govern natural resolution of inflammation is limited, especially in salivary glands (where pro-resolution pathways that promote epithelial healing remain to be identified). Recent studies demonstrate that human and animal cells convert ω-3 polyunsaturated fatty acids (PUFAs) into resolvins (Rv), which are highly potent, anti-inflammatory agents controlling the duration and magnitude of inflammation in models of colitis, periodontitis and corneal inflammation. The synthetic pathways and molecular mechanisms of Rv are similar to lipoxins (LX), the well-documented anti-inflammatory lipid mediators. Our previous studies indicate that resolvin D1 enhance epithelial integrity and block inflammatory signals caused by pro-inflammatory cytokines. Objectives: To detect whether the anti-inflammatory responses elicited by RvD1 are specific for the ALX receptor for resolvins in salivary cells. Methods: We used the ALXR antagonist Boc-2 and gene silencing approaches to study the ALXR involvement in anti-inflammatory and pro-resolution signaling responses in cell lines and in fresh isolated salivary glands. Results: the RvD1 receptor ALX/FPR2 are present in fresh isolated cells from mouse salivary glands and in cell lines of salivary origin; the agonist RvD1 (100 ng/ml) abolished TJ and cytoskeletal disruption caused by TNF-α and enhanced cell migration and polarity in salivary epithelium, these effects were blocked by the ALX/FPR2 antagonist Boc-2. Conclusions: Our results indicate that novel lipid circuits are present in salivary glands and are able to eradicate inflammation and enhance tissue integrity. These studies may have relevance in the restoration of salivary gland dysfunction associated with xerostomia.