Lipocalin2, an Innate Immune Protein, Exhibits Anti-inflammatory and Anti-Osteoclastogenic Properties
Location
Georgia
Start Date
16-5-2017 1:00 PM
Description
Lipocalin 2 (Lcn2), an innate immune protein, is known to be significantly up regulated during various inflammatory disorders including autoimmune arthritis, yet its biological role remains unclear. Recently our studies have shown an increase in the accumulation of macrophages in Lcn2 deficient mice compared to wild type (WT) mice in a serum transfer arthritic mouse model. Thus, indicating that the upregulation of Lcn2 might be necessary for the initiation and further resolution of inflammatory processes. In this study, we have investigated the anti-inflammatory function of Lcn2 using RAW 264.7 cells (murine mouse macrophages). RAW 264.7 cells treated with INFγ and LPS both exhibited pro-inflammatory phenotype, M1, while cells treated with IL-4 displayed an anti-inflammatory phenotype, M2. To determine the anti-inflammatory effects of Lcn2 an IL-10 ELISA revealed that M2 macrophages in the presence of recombinant Lcn2 (rLcn2) significantly increased the expression of IL-10. In addition, arginase-1 expression was found to be significantly upregulated in M2 polarized macrophages in the presence of rLcn2 while inducible nitric oxide synthase (iNOS) expression was down-regulated in the M1 phenotype. However, RAW 264.7 cells treated with Lcn2 alone did not exert either pro- or anti-inflammatory effect. In addition, rLcn2 inhibited the RANKL-induced osteoclast (bone resorbing cells) formation. In conclusion, Lcn2 displays the ability to significantly increase the release of anti-inflammatory cytokine, IL-10, thus promoting the anti-inflammatory properties of M2 macrophages. Collectively, our data suggests a crucial role of Lcn2 in the resolution of arthritic inflammation via macrophage polarization and directly targeting the osteoclast forming cells, making it a promising target in designing better therapeutic strategies to control the ongoing inflammation and excessive bone loss during autoimmune arthritis.
Embargo Period
6-19-2017
Lipocalin2, an Innate Immune Protein, Exhibits Anti-inflammatory and Anti-Osteoclastogenic Properties
Georgia
Lipocalin 2 (Lcn2), an innate immune protein, is known to be significantly up regulated during various inflammatory disorders including autoimmune arthritis, yet its biological role remains unclear. Recently our studies have shown an increase in the accumulation of macrophages in Lcn2 deficient mice compared to wild type (WT) mice in a serum transfer arthritic mouse model. Thus, indicating that the upregulation of Lcn2 might be necessary for the initiation and further resolution of inflammatory processes. In this study, we have investigated the anti-inflammatory function of Lcn2 using RAW 264.7 cells (murine mouse macrophages). RAW 264.7 cells treated with INFγ and LPS both exhibited pro-inflammatory phenotype, M1, while cells treated with IL-4 displayed an anti-inflammatory phenotype, M2. To determine the anti-inflammatory effects of Lcn2 an IL-10 ELISA revealed that M2 macrophages in the presence of recombinant Lcn2 (rLcn2) significantly increased the expression of IL-10. In addition, arginase-1 expression was found to be significantly upregulated in M2 polarized macrophages in the presence of rLcn2 while inducible nitric oxide synthase (iNOS) expression was down-regulated in the M1 phenotype. However, RAW 264.7 cells treated with Lcn2 alone did not exert either pro- or anti-inflammatory effect. In addition, rLcn2 inhibited the RANKL-induced osteoclast (bone resorbing cells) formation. In conclusion, Lcn2 displays the ability to significantly increase the release of anti-inflammatory cytokine, IL-10, thus promoting the anti-inflammatory properties of M2 macrophages. Collectively, our data suggests a crucial role of Lcn2 in the resolution of arthritic inflammation via macrophage polarization and directly targeting the osteoclast forming cells, making it a promising target in designing better therapeutic strategies to control the ongoing inflammation and excessive bone loss during autoimmune arthritis.