Mechanisms of disease: Regulation of RANTES (CCL5) in renal disease

Alan M. Krensky*, Yong Tae Ahn

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

85 Scopus citations

Abstract

Chemokines (chemoattractant cytokines) are fundamental regulators of immune cell movement from the bloodstream into tissues. Regulating expression of chemokines might, therefore, alleviate inflammation in autoimmune diseases and transplant rejection, or augment immune responses in cancer and immunodeficiency. RANTES (regulated upon activation, normal T cell expressed and secreted [also known as CCL5]) is a model chemokine of relevance to a myriad of diseases. Regulation of RANTES expression is complex. In fibroblasts and monocytes, rel proteins alone suffice to induce transcription of RANTES. By contrast, expression of RANTES in T lymphocytes 3-5 days after activation requires the development of a molecular complex (enhancesome) including KLF13 (Krueppel-like factor 13), rel proteins p50 and p65, and scaffolding proteins. This complex recruits enzymes involved in acetylation, methylation and phosphorylation of chromatin, and ultimately in the expression of RANTES. In addition, KLF13 - the lynchpin for recruitment of this molecular complex - is itself translationally regulated. Such complex regulation of biological systems has major implications for the rational design of drugs aimed at increasing or decreasing inflammatory responses in patients.

Original languageEnglish (US)
Pages (from-to)164-170
Number of pages7
JournalNature Clinical Practice Nephrology
Volume3
Issue number3
DOIs
StatePublished - Mar 2007

Keywords

  • CCL5
  • KLF13
  • RANTES
  • Transcription
  • Translation

ASJC Scopus subject areas

  • Nephrology

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