Lipocalin2 Mediates Anti-Inflammatory Functions Through the Inhibition of STAT3 and Activation of STAT5 Signaling in Bone Marrow Derived Macrophages
Location
Suwanee, GA
Start Date
15-5-2018 1:00 PM
Description
Lipocalin2 (Lcn2) is significantly up-regulated during various inflammatory disorders including autoimmune arthritis, however, its mechanisms are still unknown. We have shown that Lcn2-knockout (Lcn2KO) mice developed severe serum-induced arthritis (STA) compared to wild-type (WT) mice with reduced neutrophil infiltration but more macrophage migration. Therefore, in this study we have investigated the role of Lcn2 in regulating macrophages. Bone marrow derived macrophages were prepared from Lcn2KO and WT mice and polarized to inflammatory (M1) and anti-inflammatory (M2) macrophages. The polarization of M1 (iNOS) and M2 (arginase-1) phenotypes was confirmed by Western blot analysis. We did not observe a difference in polarization of Lcn2KO and WT macrophages. However, anti-inflammatory cytokines such as TGF-β1 and IL-10 were significantly reduced in IC-stimulated M2 phenotype from Lcn2KO mice than WT mice. In agreement, we observed systemically elevated pro-inflammatory cytokines in Lcn2KO (TNF-α, IL-1β and IL-6) than WT mice during STA. Further, Lcn2 deficient M1 macrophages displayed increased STAT3 activation than WT cells. In addition, WT M2 phenotype exhibited elevated STAT5 activation than Lcn2KO cells. These results suggest that Lcn2 may promote the down-regulation of pro-inflammatory but up-regulate anti-inflammatory cytokines possibly through STAT3/STAT5 signaling pathways as a negative feedback loop, limiting inflammation during autoimmune arthritis conditions.
Embargo Period
8-14-2018
Lipocalin2 Mediates Anti-Inflammatory Functions Through the Inhibition of STAT3 and Activation of STAT5 Signaling in Bone Marrow Derived Macrophages
Suwanee, GA
Lipocalin2 (Lcn2) is significantly up-regulated during various inflammatory disorders including autoimmune arthritis, however, its mechanisms are still unknown. We have shown that Lcn2-knockout (Lcn2KO) mice developed severe serum-induced arthritis (STA) compared to wild-type (WT) mice with reduced neutrophil infiltration but more macrophage migration. Therefore, in this study we have investigated the role of Lcn2 in regulating macrophages. Bone marrow derived macrophages were prepared from Lcn2KO and WT mice and polarized to inflammatory (M1) and anti-inflammatory (M2) macrophages. The polarization of M1 (iNOS) and M2 (arginase-1) phenotypes was confirmed by Western blot analysis. We did not observe a difference in polarization of Lcn2KO and WT macrophages. However, anti-inflammatory cytokines such as TGF-β1 and IL-10 were significantly reduced in IC-stimulated M2 phenotype from Lcn2KO mice than WT mice. In agreement, we observed systemically elevated pro-inflammatory cytokines in Lcn2KO (TNF-α, IL-1β and IL-6) than WT mice during STA. Further, Lcn2 deficient M1 macrophages displayed increased STAT3 activation than WT cells. In addition, WT M2 phenotype exhibited elevated STAT5 activation than Lcn2KO cells. These results suggest that Lcn2 may promote the down-regulation of pro-inflammatory but up-regulate anti-inflammatory cytokines possibly through STAT3/STAT5 signaling pathways as a negative feedback loop, limiting inflammation during autoimmune arthritis conditions.