IADR Abstract Archives
ALX/FPR2 modulates anti-inflammatory responses in mouse submandibular gland
Objectives: Activation of the G-protein coupled formyl peptide receptor 2 (ALX/FPR2) by the lipid mediators lipoxin A4 and resolvin D1 (RvD1) promotes resolution of inflammation. Our previous studies indicate that activation of the ALX/FPR2 with RvD1 leads to resolution of cytokine-mediated inflammatory responses in salivary cells. However, the in vivo impact of the ALX/FPR2 on salivary gland function is unknown. To determine whether submandibular glands (SMG) from ALX/FPR2 -/- mice display altered pro-inflammatory responses to lipopolysaccharides (LPS) stimulation.
Methods: 12-week-old control C57BL/6 and ALX/FPR2 -/- mice were treated with LPS (10 mg/kg) for 24 h and then SMG were removed and analyzed for histopathological changes using H&E staining of paraffin sections and for the inflammatory cytokine profile using quantitative PCR and western blotting. Finally, the saliva secretion rate was determined in response to pilocarpine 10 mg pilocarpine-HCl/kg body weight.
Results: LPS induced severe lymphocytic infiltration in the SMG from ALX/FPR2 -/- as compared to C57BL/6 mice. Moreover, quantitative PCR results showed a severe pro-inflammatory response in ALX/FPR2 -/- mice as compared to C57BL/6. Finally, we found that the mRNA expression of the Muscarinic acetylcholine receptor M3 (M3R) and saliva production were both impaired in the ALX/FPR2 -/- mice upon LPS-induction. Male and female ALX/FPR2 -/- mice showed similar responses to LPS.
Conclusions: Our data suggest that unresolved pro-inflammatory responses due to the loss of ALX/FPR2 results in SMG dysfunction, causing xerostomia (dry mouth symptom) that partially resembles Sjögren’s syndrome. Overall, we conclude that ALX/FPR2 plays an important role in the in vivo resolution of LPS-mediated inflammation of SMG.
Methods: 12-week-old control C57BL/6 and ALX/FPR2 -/- mice were treated with LPS (10 mg/kg) for 24 h and then SMG were removed and analyzed for histopathological changes using H&E staining of paraffin sections and for the inflammatory cytokine profile using quantitative PCR and western blotting. Finally, the saliva secretion rate was determined in response to pilocarpine 10 mg pilocarpine-HCl/kg body weight.
Results: LPS induced severe lymphocytic infiltration in the SMG from ALX/FPR2 -/- as compared to C57BL/6 mice. Moreover, quantitative PCR results showed a severe pro-inflammatory response in ALX/FPR2 -/- mice as compared to C57BL/6. Finally, we found that the mRNA expression of the Muscarinic acetylcholine receptor M3 (M3R) and saliva production were both impaired in the ALX/FPR2 -/- mice upon LPS-induction. Male and female ALX/FPR2 -/- mice showed similar responses to LPS.
Conclusions: Our data suggest that unresolved pro-inflammatory responses due to the loss of ALX/FPR2 results in SMG dysfunction, causing xerostomia (dry mouth symptom) that partially resembles Sjögren’s syndrome. Overall, we conclude that ALX/FPR2 plays an important role in the in vivo resolution of LPS-mediated inflammation of SMG.
