Extracellular matrix of early pulmonary fibrosis modifies the polarization of alveolar macrophage.

Yanwei Zhang, Lihua Zhu, Jinsheng Hong, Chun Chen

International immunopharmacology 2022 Oct

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Macrophage polarization is modulated by many different stimuli. However, the effect of fibrotic extracellular matrix (ECM) on macrophage polarization remains unclear. In this study, a mouse model of radiation induced pulmonary fibrosis (RIPF) was established. Alveolar macrophages (AMs) were seeded on separated decellularized ECM respectively derived from early RIPF lung tissue (dECM-RIPF) and normal lung tissue (dECM-Nor), on which the polarization of AMs was examined. By way of bio-AFM analysis, a significant difference in surface roughness, but no difference in stiffness, was found between dECM-RIPF and dECM-Nor. Compared with dECM-Nor, dECM-RIPF induced a higher M1 activation and increased the levels of TNF-α, IL-6 and IL-1β, while it showed no significant effect M2 density. Nevertheless, such effects induced by dECM-RIPF could be abrogated by the integrin pan-inhibitor. Furthermore, dECM-RIPF caused integrin-dependent activation of NFκB, and NFκB inhibitor was capable of inhibiting dECM-RIPF-induced AMs proliferation and M1 activation. Animal experiments showed that NFκB inhibitor alleviated RIPF mainly through inhibiting M1 activation and down-regulating the levels of inflammatory cytokines. Our results showed that differential biophysical signaling from the fibrotic ECM of early RIPF promoted AMs polarization towards a M1 phenotype via integrin-NFκB. Inhibition of M1 activation may be an attractive approach for treating RIPF. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Yanwei Zhang, Lihua Zhu, Jinsheng Hong, Chun Chen. Extracellular matrix of early pulmonary fibrosis modifies the polarization of alveolar macrophage. International immunopharmacology. 2022 Oct;111:109179