Translating Inflammation

Abstract

Neutrophils are key cells involved in immune responses, which link the innate and adaptive immune systems and release various inflammatory mediators when stimulated. Lindemann et al. report that there is a pronounced increase in the abundance of many proteins in neutrophils in response to the phospholipid mediator platelet-activating factor (PAF). However, it is known that neutrophils do not exhibit a robust change in the abundance of many mRNAs when stimulated, which suggests a posttranscriptional mechanism for regulating protein abundance. Detailed analysis of the increase in abundance of IL-6Rα (interleukin 6 receptor α), a protein that contributes to IL-6 signaling either in a membrane-bound form or soluble form, showed that this increase was not accompanied by an increase in mRNA and was inhibited by drugs that block translation, but not those that block transcription. Analysis of the 5′ untranslated region of the IL-6Rα mRNA suggested that translation could be controlled by the mTOR pathway, which stimulates translation machinery in response to signals that stimulate the phosphoinositide 3-kinase pathway. The involvement of the mTOR pathway was verified by blockade of the response to PAF with rapamycin, an inhibitor of mTOR. Thus, these transcriptionally quiet immune cells can still regulate protein abundance by stimulating translation through the mTOR pathway. S. W. Lindemann, C. C. Yost, M. M. Denis, T. M. McIntyre, A. S. Weyrich, G. A. Zimmerman, Neutrophils alter the inflammatory milieu by signal-dependent translation of constitutive messenger RNAs. Proc. Natl. Acad. Sci. U.S.A. 101 , 7076-7081 (2004). [Abstract] [Full Text]