Abstract
Previous studies demonstrated that activation of the mouse G protein-coupled formyl peptide receptor 2 (mFpr2) with aspirin-triggered resolvin D1 (AT-RvD1) blocks pro-inflammatory cytokine signaling while promoting salivary gland (SG) epithelial integrity both in vitro and in vivo. In addition, mice lacking Fpr2 display alterations of SG innate and adaptive immunity. Taken together, these results indicate that Fpr2 activation with AT-RvD1 restores saliva secretion and regulates SG immunity in mice. To demonstrate the value of AT-RvD1 for use in human SG, however, we need to extend the findings above in the direction of clinical use. To this end, the current study investigated whether treatment with AT-RvD1 reduces SG inflammation and restores saliva secretion in an acute sialadenitis mouse model expressing the human formyl peptide receptor 2 (hFPR2) protein. Results indicate that mice carrying the hFPR2 and treated with lipopolysaccharide (LPS) display acute sialadenitis-like features as shown by increased levels of proliferating inflammatory cells, loss of epithelial integrity and reduced saliva secretion. In contrast, when these mice are treated with AT-RvD1, the sialadenitis-like features are drastically reduced as evidenced by a significant decrease in proliferating inflammatory cells as well as restoration of saliva secretion to levels comparable to phosphate buffered saline (PBS)-treated healthy controls. Finally, changes observed in mice carrying the hFPR2 and treated with LPS and AT-RvD1 were comparable to those observed in wild-type mice carrying the mFpr2. Together, these results demonstrate that activation of hFPR2 with AT-RvD1 resolves acute sialadenitis in vivo.