THU0015 VARIATION IN MACROPHAGES DIFFERENTIATION AND SREBF1 EXPRESSION BETWEEN INFRAPATELLAR FAT PAD AND SUBCUTANEOUS TISSUES FROM RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS PATIENTS
Authors: Shuhe Ma, Kosaku Murakami, Motomu Hashimoto, Masao Tanaka, Koichi Murata, Kohei Nishitani, Hiromu Ito, Tsuneyo Mimori
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Sterol regulatory element-binding protein 1 (SREBP1) has been known to upregulate the expression levels of regulators of ω-3 fatty acids in the resolution phase of macrophages, and this would in turn repress the production of pro-inflammatory cytokines.<sup>[1, 2]</sup> In OA joints, adipocytes might participate in inflammatory process.<sup>[3]</sup> We are interested in the proportion of M1 and M2 macrophages in stromal vascular fraction (SVF) from both tissues in both diseases. And to investigate how <i>srebf1</i> works in infrapatellar fat pad (IFP, or Hoffa) or subcutaneous (SC) tissue, we studied the expression levels of <i>srebf1</i>, pro-inflammatory cytokines and regulators of fatty acids. <h3>Objectives:</h3> To investigate the proportion of CD14 positive cells as well as M1 and M2 macrophages in SVF of Hoffa and SC; and to explore contribution of SREBP1 to rheumatic disease pathological processes of RA and OA. <h3>Methods:</h3> After treated with collagenase, macrophages (CD14 positive cells) in SVF were counted by flow cytometry. Then they were divided, half for calculating the ratio between CD80 positive cells (M1 macrophages) and CD163 positive cells (M2 macrophages), and half for performing qRT-PCR. <h3>Results:</h3> Characteristics of the patients OA: osteoarthritis; RA: rheumatoid arthritis; CRP: C-reactive protein; BMI: body mass index; BMI: &lt;18,5 underweight; BMI: 18.5–24.99 normal; BMI: 25.0–29.99 overweight; BMI &gt;30.0 obesity<sup>[4]</sup> More CD14 positive cells exist in Hoffa comparing to SC, and M2 macrophages show higher proportion. A comparison of proportion of CD14 positive cells between Hoffa and SC showed significance both from OA and from RA. To M2 macrophages proportion, higher percentages of M2 macrophages (OA: 26.3±5.5%, RA: 22.5±2.4%) exist in Hoffa from both OA and RA patients, but no significance was found between the diseases. However, the proportion of M1 macrophages (OA: 15.6±1.7%, RA: 11.3±2.1%) indicated significance. <i>Srebf1</i> expressed less in Hoffa than in SC Results show that in Hoffa, <i>srebf1c</i> expressed less in RA patients than that in OA patients, but no significance was indicated. In the comparison of expression levels between Hoffa and SC, both <i>srebf1a</i> and <i>srebf1c</i> showed significance, and more <i>IL-6</i> and <i>IL-1β</i> expressed in Hoffa than in SC. <h3>Conclusion:</h3> In RA patients, more M2 macrophages exist in Hoffa than in SC. Lower expression levels of <i>srebf1c</i> in Hoffa from RA patients suggests that macrophages differentiation can be reprogrammed by fatty acid metabolism. <h3>References:</h3> [1] Oishi, Y., et al., Cell Metab, 2017. 25(2): p. 412-427 [2] Shimano, H. and R. Sato, Nat Rev Endocrinol, 2017. 13(12): p. 710-730. [3] Shimano, H., et al., The Journal of Clinical Investigation, 1997. 99(5): p. 846-854. [4] Plebanczyk, M., et al., Inflammation, 2018. <h3>Disclosure of Interests:</h3> Shuhe Ma: None declared, Kosaku Murakami: None declared, Motomu Hashimoto Grant/research support from: Astellas, Brystol-Meyers, Eisai, Employee of: M. H. is affiliated with the department (Department of Advanced Medicine for Rheumatic Diseases, Kyoto University), which is financially supported by four pharmaceutical companies (Tanabe-Mitsubishi, Chugai, Ayumi, UCB Japan), Speakers bureau: Tanabe Mitsubishi, Brystol-Meyers, Masao Tanaka: None declared, Koichi Murata: None declared, Kohei Nishitani: None declared, Hiromu Ito: None declared, Tsuneyo Mimori: None declared