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Modulation of Mouse Macrophage Polarization in Vitro Using IL-4 Delivery by Osmotic Pumps

Jukka Pajarinen, Yasunobu Tamaki, Joseph K Antonios, Tzu-Hua Lin, Taishi Sato, Zhenyu Yao, Michiaki Takagi, Yrjö T Konttinen, Stuart B Goodman

J Biomed Mater Res A. 2015 Apr;103(4):1339-45.

PMID: 25044942

Abstract:

Modulation of macrophage polarization is emerging as promising means to mitigate wear particle-induced inflammation and periprosthetic osteolysis. As a model for continuous local drug delivery, we used miniature osmotic pumps to deliver IL-4 in order to modulate macrophage polarization in vitro from nonactivated M0 and inflammatory M1 phenotypes towards a tissue regenerative M2 phenotype. Pumps delivered IL-4 into vials containing mouse bone marrow macrophage (mBMM) media. This conditioned media (CM) was collected at seven day intervals up to four weeks (week 1 to week 4 samples). IL-4 concentration in the CM was determined by ELISA and its biological activity was assayed by exposing M0 and M1 mBMMs to week 1 or week 4 CM. The IL-4 concentration in the CM approximated the mathematically calculated amount, and its biological activity was well retained, as both M0 and M1 macrophages exposed to either the week 1 or week 4 CM assumed M2-like phenotype as determined by qRT-PCR, ELISA, and immunocytochemistry. The results show that IL-4 can be delivered using osmotic pumps and that IL-4 delivered can modulate macrophage phenotype. Results build a foundation for in vivo studies using our previously validated animal models and provide possible strategies to locally mitigate wear particle-induced macrophage activation and periprosthetic osteolysis.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42413411 IL-4 from mouse IL-4 from mouse Price
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