title: Attenuated expression of interferon-β and interferon-λ1 by human alternatively activated macrophages.
abstract: Macrophages can be polarized into classically (CAM) or alternatively (AAM) activated macrophages with IFN-γ or IL-4, respectively. CAM are associated with type 1 immune responses and are implicated in autoimmunity; AAM are associated with type 2 responses and are implicated in allergic diseases. An impediment in investigating macrophage biology using primary human monocyte derived macrophages is the wide inter-donor heterogeneity and the limited quantity of cells that survive in vitro polarization. To overcome this impediment, we established a protocol to generate CAM and AAM cultures derived from the THP-1 human promonocytic cell line. In this report, we demonstrate that THP-CAM and -AAM express gene and protein markers that define their primary human monocyte derived counterparts, such as IL-1β, CXCL10, and CXCL11 for CAM, and MRC1, IL-4 and CCL22 for AAM. In addition, we demonstrate that STAT6 is selectively activated in THP-AAM which, upon LPS stimulation, have an attenuated or delayed expression of IFN-β, IFN-λ1, and IFN α/β pathway genes compared to their CAM counterparts. Taken together, these findings may help further investigate human diseases associated with the alternatively activated macrophage phenotype using this reproducible in vitro macrophage model.
authors.affiliation: Laboratory of Immunobiochemistry, Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, 29 Lincoln Drive, Bethesda, MD 20892-4555, USA.
authors.forename: Ashraf
authors.initials: A
authors.lastname: El Fiky
authors.forename: Roger
authors.initials: R
authors.lastname: Perreault
authors.forename: Gwendolyn J
authors.initials: GJ
authors.lastname: McGinnis
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Rabin
mesh_terms: D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016899:Interferon-beta; D007371:Interferon-gamma
keywords: AAM; BAL; CAM; IFN; ISGs; LPS; MD; PMA; RV; alternatively activated macrophages; bronchoalveolar lavage; classically activated macrophages; interferon; interferon stimulated genes; lipopolysaccharide; phorbol-12-myristate-13-acetate; primary human monocyte derived macrophages; rhinovirus