Osthole Attenuates Macrophage Activation in Experimental Asthma by Inhibitingthe NF-ĸB/MIF Signaling Pathway

• Published in: Frontiers in pharmacology Vol. 12; p. 572463
• Main Authors: Li, Ruyi, Song, Peng, Tang, Guofang, Wei, Jianghong, Rao, Lizong, Ma, Libing, Jiang, Ming, Huang, Jianwei, Xu, Qing, Wu, Jingjie, Lv, Qian, Yao, Dong, Xiao, Bo, Huang, Haiming, Lei, Liping, Feng, Juntao, Mo, Biwen
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22-03-2021
• Subjects: asthma; macrophages; MIF 46; NF-ĸB; osthole; Pharmacology; MIF 46; macrophages; asthma; NF-ĸB; osthole
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2021.572463

Inhibition of activated macrophages is an alternative therapeutic strategy for asthma. We investigated whether a coumarin compound, osthole, isolated from
(L.) Cuss, alleviated macrophage activation
and
. Osthole could reduce expression of a marker of activated macrophages, cluster of differentiation (CD)206, in an ovalbumin-challenge model of asthma in mice. Osthole could also inhibit infiltration of inflammatory cells, collagen deposition and production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-ɑ, macrophage migration inhibitory factor (MIF)] in asthmatic mice.
, expression of phosphorylated-IĸBɑ, MIF and M2 cytokines (Ym-1, Fizz-1, arginase-1) in IL-4-induced macrophages decreased upon exposure to the NF-ĸB inhibitor MG-132. In our short hairpin (sh)RNA-MIF-knockdown model, reduced expression of M2 cytokines was detected in the IL-4 + shRNA-MIF group. Osthole could attenuate the proliferation and migration of an IL-4-induced rat alveolar macrophages line (NR8383). Osthole could reduce IL-4-induced translocation of nuclear factor-kappa B (NF-ĸB) in NR8383 cells. Collectively, our results suggest that osthole ameliorates macrophage activation in asthma by suppressing the NF-ĸB/MIF signaling pathway, and might be a potential agent for treating asthma.