Poster Topical Area: Nutritional Immunology

Location: Hall D

Poster Board Number: 843

P21-012 - Asaronic acid promotes M1 to M2-phenotype shift by prostaglandin E2 and inhibits M2 to M1 transition by high glucose in LPS or IL-4 exposed macrophages

Sunday, Jun 10
8:00 AM – 6:00 PM

Objectives:Macrophage inflammation is a critical event during the initiation and development of atherosclerosis. M1 macrophages are accumulated the progressing plaque and M2 macrophages are promoted to regressing plaque. In atherosclerotic lesions, macrophages responsive to various stimuli can result in their functional phenotype shifts. Also, insulin resistance is promoted by a transition in macrophage polarization from an alternative M2 to a classical M1.This study examined whether asaronic acid (2,4,5-Trimethoxybenzoic acid), identified as one of purple perilla constituents, enhanced M1 to M2-phenotype shift and blocked M2 to M1 transition.

 
Methods:
J774A1 murine macrophages were incubated with 2 μg/ml lipopolysaccharide (LPS) or 40 ng/ml interleukin (IL)-4 in the absence and presence of 1-20 μΜ asaronic acid with anti-allergic and anti-oxidant effects. LPS-exposed J774A1 macrophages were incubated with prostaglandin E2(PGE2) and asaronic acid, and IL-4-exposed macrophages were treated with 33 mM glucose in the presence of asaronic acid. The induction of the M1 and M2 cytokines and biomarkers was measured by using ELISA kits and Western-blotting with specific antibodies.

 
Results:
Non-toxic asaronic acid at ≤20 μM dampened the secretion of toll-like receptor 4 in macrophages exposed to 2 μg/ml LPS for 48h. In addition, asaronic acid suppressed the induction of the M1 markers of IL-6, CD68 and CD36 enhanced by LPS. On the contrary, ≤20μM asaronic acid further enhanced the macrophage induction of the M2 markers of CD163 and arginase-1 (Arg-1) inducted by IL-4.On the other hand, asaronic acid promoted the secretion of Arg-1 by 24 h-incubation of PGE2 in M1 macrophages exposed to LPS. High glucose increased transition into the M1 phenotype from IL-4-exposed M2 macrophages.

 
Conclusion:
These results demonstrated that asaronic acid promoted M1 to M2-phenotype shift following exposure to PGE2, whereas this compound inhibited the functional transition of M2 macrophages by high glucose. Thus, asaronic acid has therapeutic potential in inflammation and diabetes possibly through modulating the polarization of M1/M2 macrophages.


CoAuthors: Sin-Hye Park – Hallym university; Young-Hee Kang – Hallym university

Hyeongjoo Oh


Hallym university
Chuncheong-si, Kangwon-do, Republic of Korea