Y.-W., Lin B., Lee P.-S., Liu L.-N., Wei Supplementary Material for: Receptor-Interacting Protein 140 Orchestrates the Dynamics of Macrophage M1/M2 Polarization Macrophage classical (M1) versus alternative (M2) polarization is critical for the homeostatic control of innate immunity. Uncontrolled macrophage polarization is frequently implicated in diseases. This study reports a new functional role for receptor-interacting protein 140 (RIP140) in regulating this phenotypic switch. RIP140 is required for M1 activation, and its degradation is critical to LPS-induced endotoxin tolerance (ET). Here, we found that failure to establish RIP140 degradation-mediated ET prevents M2 polarization, and reducing RIP140 level facilitates an M1/M2 switch, resulting in more efficient wound healing in animal models generated with either transgenic or bone marrow transplant procedures. The M2-suppressive effect is elicited by a new function of RIP140 that, in macrophages exposed to M2 cues, is exported to cytosol, forming complexes with CAPNS1 (calpain regulatory subunit) to activate calpain 1/2, that activates PTP1B phosphatase. The activated PTP1B then reduces STAT6 phosphorylation, thereby suppressing the efficiency of M2 polarization. It is concluded that RIP140 plays dual roles in regulating the M1-M2 phenotype switch: the first, in the nucleus, is an M1 enhancer and the second, in the cytosol, is an M2 suppressor. Modulating the level and/or subcellular distribution of RIP140 can be a new therapeutic strategy for diseases where inflammatory/anti-inflammatory responses are critical. Receptor-interacting protein 140;STAT6;Wound healing;Inflammation;Endotoxin tolerance;PTP1B;Macrophage polarization 2015-07-23
    https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Receptor-Interacting_Protein_140_Orchestrates_the_Dynamics_of_Macrophage_M1_M2_Polarization/5128261
10.6084/m9.figshare.5128261.v1