Abstract
Naturally occurring polyamines are ubiquitously distributed and play important roles in cell development, amino acid and protein synthesis, oxidative DNA damage, proliferation, and cellular differentiation. Macrophages are essential in the innate immune response, and contribute to tissue remodeling. Naïve macrophages have two major potential fates: polarization to (1) the classical pro-inflammatory M1 defense response to bacterial pathogens and tumor cells, and (2) the alternatively activated M2 response, induced in the presence of parasites and wounding, and also implicated in the development of tumor-associated macrophages. ODC, the rate-limiting enzyme in polyamine synthesis, leads to an increase in putrescine levels, which impairs M1 gene transcription. Additionally, spermidine and spermine can regulate translation of pro-inflammatory mediators in activated macrophages. In this review, we focus on polyamines in macrophage activation patterns in the context of gastrointestinal inflammation and carcinogenesis. We seek to clarify mechanisms of innate immune regulation by polyamine metabolism and potential novel therapeutic targets.
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We thank the members of the Wilson Lab for their work related to the original research summarized in this article.
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This work was funded by NIH Grants R01AT004821, R01CA190612, P01CA116087, and P01CA028842 (K.T.W.), Merit Review Grant I01BX001453 from the United States Department of Veterans Affairs Biomedical Laboratory R&D (BLRD) Service (K.T.W.), the Vanderbilt Digestive Disease Research Center, supported by NIH Grant P30DK058404, the Vanderbilt Ingram Cancer Center, supported by NIH Grant P30CA068485, Department of Defense Grant W81XWH-18-1-0301 (K.T.W.), the Thomas F. Frist Sr. Endowment (K.T.W.), and the Vanderbilt Center for Mucosal Inflammation and Cancer (K.T.W.).
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Latour, Y.L., Gobert, A.P. & Wilson, K.T. The role of polyamines in the regulation of macrophage polarization and function. Amino Acids 52, 151–160 (2020). https://doi.org/10.1007/s00726-019-02719-0
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DOI: https://doi.org/10.1007/s00726-019-02719-0