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      The Kinase Akt1 Controls Macrophage Response to Lipopolysaccharide by Regulating MicroRNAs

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          Abstract

          MicroRNAs regulated by lipopolysaccharide (LPS) target genes that contribute to the inflammatory phenotype. Here, we showed that the protein kinase Akt1, which is activated by LPS, positively regulated miRNAs let-7e and miR-181c but negatively regulated miR-155 and miR-125b. In silico analyses and transfection studies revealed that let-7e repressed Toll-like receptor 4 (TLR4), whereas miR-155 repressed SOCS1, two proteins critical for LPS-driven TLR signaling, which regulate endotoxin sensitivity and tolerance. As a result, Akt1(-/-) macrophages exhibited increased responsiveness to LPS in culture and Akt1(-/-) mice did not develop endotoxin tolerance in vivo. Overexpression of let-7e and suppression of miR-155 in Akt1(-/-) macrophages restored sensitivity and tolerance to LPS in culture and in animals. These results indicate that Akt1 regulates the response of macrophages to LPS by controlling miRNA expression.

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          Author and article information

          Journal
          Immunity
          Immunity
          Elsevier BV
          10747613
          August 2009
          August 2009
          : 31
          : 2
          : 220-231
          Article
          10.1016/j.immuni.2009.06.024
          2865583
          19699171
          9f2e994a-49c7-402a-be05-3a76ca2c8d19
          © 2009

          https://www.elsevier.com/tdm/userlicense/1.0/

          https://www.elsevier.com/open-access/userlicense/1.0/

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