biostudies-literatureAyaub EAOntario Thoracic SocietyEva Eugenia Lillian Cope GraduateOntario Graduate ScholarshipsCIHR203-217https://www.ebi.ac.uk/biostudies/studies/S-EPMC7379543biostudies-literatureUnknown97(2)Although recent evidence has shown that IL-6 is involved in enhanced alternative activation of macrophages toward a profibrotic phenotype, the mechanisms leading to their increased secretory capacity are not fully understood. Here, we investigated the effect of IL-6 on endoplasmic reticulum (ER) expansion and alternative activation of macrophages in vitro. An essential mediator in this ER expansion process is the IRE1 pathway, which possesses a kinase and endoribonuclease domain to cleave XBP1 into a spliced bioactive molecule. To investigate the IRE1-XBP1 expansion pathway, IL-4/IL-13 and IL-4/IL-13/IL-6-mediated alternative programming of murine bone marrow-derived and human THP1 macrophages were assessed by arginase activity in cell lysates, CD206 and arginase-1 expression by flow cytomImmunology and cell biologyIL-6 mediates ER expansion during hyperpolarization of alternatively activated macrophages.PMC7379543137013140358Dickhout JGUpagupta CAyaub EATandon KDvorkin-Gheva APadwal MDubey ALhotak SMekhael OAyoub ARichards CDAsk KImani JKolb MRJKolb PSAustin RCMurphy JPatel HfalseIL-6 mediates ER expansion during hyperpolarization of alternatively activated macrophages.Although recent evidence has shown that IL-6 is involved in enhanced alternative activation of macrophages toward a profibrotic phenotype, the mechanisms leading to their increased secretory capacity are not fully understood. Here, we investigated the effect of IL-6 on endoplasmic reticulum (ER) expansion and alternative activation of macrophages in vitro. An essential mediator in this ER expansion process is the IRE1 pathway, which possesses a kinase and endoribonuclease domain to cleave XBP1 into a spliced bioactive molecule. To investigate the IRE1-XBP1 expansion pathway, IL-4/IL-13 and IL-4/IL-13/IL-6-mediated alternative programming of murine bone marrow-derived and human THP1 macrophages were assessed by arginase activity in cell lysates, CD206 and arginase-1 expression by flow cytom2019-01-01T00:00:00Z2019 Feb2025-04-05T13:44:22.441Z2025-04-05T13:44:22.441ZS-EPMC73795433029895210.1111/imcb.12212