Attenuated expression of interferon-beta and interferon-lambda l by human alternatively activated macrophages

作者：El Fiky Ashraf; Perreault Roger; McGinnis Gwendolyn J; Rabin Ronald L^*

来源：Human Immunology, 2013, 74(12): 1524-1530.

DOI：10.1016/j.humimm.2013.08.267

Macrophages can be polarized into classically (CAM) or alternatively (MM) activated macrophages with IFN-gamma 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 -AMM express gene and protein markers that define their primary human monocyte derived counterparts, such as IL-1 beta, CXCL10, and CXCL11 for CAM, and MRC1, IL-4 and CCL22 for AMM. In addition, we demonstrate that STAT6 is selectively activated in THP-AMM which, upon LPS stimulation, have an attenuated or delayed expression of IFN-beta, IFN-lambda 1, and IFN alpha/beta 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.

• 出版日期2013-12