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Interleukin‐6 and cyclooxygenase‐2 mediate myofibroblast‐induced polarization of alternatively activated macrophages (734.9)
Author(s) -
Fernando Maria,
McKay Derek
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.734.9
Subject(s) - myofibroblast , cyclooxygenase , in vivo , wound healing , macrophage polarization , chemistry , nitric oxide synthase , macrophage , nitric oxide , inflammation , bone marrow , microbiology and biotechnology , immunology , in vitro , cancer research , pathology , medicine , biology , biochemistry , enzyme , organic chemistry , fibrosis
Alternatively activated macrophages (AAMΦs) are a macrophage subset induced primarily by the Th2 cytokines IL‐4 and IL‐13. They are associated with anti‐inflammatory functions, such as wound healing and tissue repair and are also protective in animal models of diseases, such as inflammatory bowel disease and multiple sclerosis. In this study we showed that myofibroblasts, also associated with wound healing, may have a putative in vivo role in the induction and maintenance of AAMΦs. Macrophages and myofibroblasts (MFbs) were derived from murine bone marrow and dermal tissue (wild‐type and IL‐6 ‐/‐ ), respectively. MΦ were exposed to IL‐4+IL‐13 conditioned medium (CM) from control MFbs or MFbs treated with a non‐selective cyclooxygenase (COX)‐1 and ‐2 inhibitor (indomethacin) or a selective COX‐1 (SC‐560) or COX‐2 inhibitor (NS‐398). Exposure to control MFb CM enhanced markers of AAMΦ polarization and reduced LPS‐evoked nitric oxide release. These effects were partially reduced using MFbs from IL‐6 ‐/‐ mice, suggesting a role for IL‐6 in this process. CM from indomethacin‐ and NS‐398‐treated MFbs failed to enhance an AAMΦ phenotype ‐ SC‐560 did not have this same effect. Inhibition of EP4 on MΦ also eliminated the effect of MFb CM, implicating PGE 2 . These data indicate a role for IL‐6 and PGE 2 , two molecules commonly linked with pro‐inflammatory functions, in the differentiation of anti‐inflammatory AAMΦs. Grant Funding Source : CCFC, CIHR, CDHF, AIHS