Title

The Role of Lipocalin 2, an Innate Immune Protein During Auto Inflammatory Disorders

Date of Award

2020

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Vishakha Bhave, BS, PhD

Second Advisor

Srujana Rayalam, PhD

Third Advisor

Bonnie Buxton, PhD

Fourth Advisor

Rangaiah Shashidharamurthy, PhD

Abstract

Lipocalin 2 (Lcn2), a 25KDa innate immune protein, is known to be dramatically up regulated in various inflammatory disorders including antibody-mediated arthritis, yet its biological role remains unclear. More 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 up regulation 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 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 rLcn2 significantly increased the expression of IL-10. In addition, Arginase-1 expression was found to be significantly up regulated in M2 polarized macrophages in the presence of rLcn2 while INOS 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 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, making it a promising target in designing better therapeutic strategies to control the ongoing inflammation during autoimmune arthritis.

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