PGRN Relieves Inflammation By Supressed Macrophages Recruitment Through CCL2 In Atute Otitis Media

Background:Acute otitis media(AOM)is one of the most common pediatric infections,over 80% of children will develop OM at least once before 3 years of age.PGRN(progranulin)is likewise expressed in a broad range of other tissues and cell types.PGRN has multiple physiological functions and is involved in many types of disease processes,including autoimmune disorders,cancer,and neurodegenerative diseases.Recent studies show that PGRN has relationship with inflammation.PGRN bound directly to tumor necrosis factor receptors(TNFR)and disturbed the TNFα/TNFR interaction,which suggested new potential therapeutic interventions for various TNFα-mediated pathologies and conditions.Methods :We developed a model of AOM following tansbullar injection to C57BL/6 mice and PGRN-/-mice.Percentages of neutrophils and macrophages were evaluated by FCM.Concentrations of cytokines and chemokines were analyzed by ELISA methods.The ME tissues were collected for HE and immunohistochemical staining.Results : Expression of PGRN was found in S.pn induced MELF(mouse ear lavage fluid).Campared with WT mice,the absence of PGRN impaired S.pn clearance and leaded to more severe inflammation.CCL2 was inceased most significantly in ME,which contributes to recuit macrophages.Administration of PGRN both rescued impaired host defense and suppressed inflammation.Conclision: These data support the conclusion that PGRN inhibiting the inflammation by decreasing the recruitment of macrophges through CCL2.