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S100A9 as a pharmacological target molecule in inflammation and cancer.

Leanderson, Tomas LU ; Liberg, David LU and Ivars, Fredrik LU (2015) In Endocrine, Metabolic & Immune Disorders - Drug Targets 15(2). p.97-104
Abstract
Upon tissue injury and infection both stressed and dying cells can release proteins that normally reside inside the cells. Some of the released proteins become ligands of various cell surface receptors expressed by local cells and such proteins are denoted damage associated molecular patterns (DAMPs). Binding of some DAMPs to certain cell surface receptors induces signals emanating in the production of pro-inflammatory cytokines, ultimately leading to an inflammatory response. Our laboratory is interested in the S100A9 protein, a bona fide DAMP protein. This protein normally resides inside monocytes and neutrophils and in these cells it forms heterodimers with the S100A8 protein. The S100A8/A9 heterodimer is released in large amounts... (More)
Upon tissue injury and infection both stressed and dying cells can release proteins that normally reside inside the cells. Some of the released proteins become ligands of various cell surface receptors expressed by local cells and such proteins are denoted damage associated molecular patterns (DAMPs). Binding of some DAMPs to certain cell surface receptors induces signals emanating in the production of pro-inflammatory cytokines, ultimately leading to an inflammatory response. Our laboratory is interested in the S100A9 protein, a bona fide DAMP protein. This protein normally resides inside monocytes and neutrophils and in these cells it forms heterodimers with the S100A8 protein. The S100A8/A9 heterodimer is released in large amounts during several types of inflammatory disease and is currently used clinically as a biomarker in some diseases. The fact that several different pro-inflammatory functions have been ascribed to this protein makes it a potential target for the development of small molecule inhibitors. We have developed several such inhibitors, some of which are already in phase III clinical development. This review describes our efforts to investigate the biological functions of the S100A9 protein as well as our ongoing efforts of developing second-generation, more specific, small molecule inhibitors of its pro-inflammatory functions. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Endocrine, Metabolic & Immune Disorders - Drug Targets
volume
15
issue
2
pages
97 - 104
publisher
Bentham Science Publishers
external identifiers
  • pmid:25772177
  • wos:000355000200004
  • scopus:84930519540
ISSN
2212-3873
language
English
LU publication?
yes
id
64deef3f-10b4-4bd2-9f4a-f47683a59449 (old id 5258648)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25772177?dopt=Abstract
date added to LUP
2015-04-03 19:59:58
date last changed
2017-08-13 03:21:52
@article{64deef3f-10b4-4bd2-9f4a-f47683a59449,
  abstract     = {Upon tissue injury and infection both stressed and dying cells can release proteins that normally reside inside the cells. Some of the released proteins become ligands of various cell surface receptors expressed by local cells and such proteins are denoted damage associated molecular patterns (DAMPs). Binding of some DAMPs to certain cell surface receptors induces signals emanating in the production of pro-inflammatory cytokines, ultimately leading to an inflammatory response. Our laboratory is interested in the S100A9 protein, a bona fide DAMP protein. This protein normally resides inside monocytes and neutrophils and in these cells it forms heterodimers with the S100A8 protein. The S100A8/A9 heterodimer is released in large amounts during several types of inflammatory disease and is currently used clinically as a biomarker in some diseases. The fact that several different pro-inflammatory functions have been ascribed to this protein makes it a potential target for the development of small molecule inhibitors. We have developed several such inhibitors, some of which are already in phase III clinical development. This review describes our efforts to investigate the biological functions of the S100A9 protein as well as our ongoing efforts of developing second-generation, more specific, small molecule inhibitors of its pro-inflammatory functions.},
  author       = {Leanderson, Tomas and Liberg, David and Ivars, Fredrik},
  issn         = {2212-3873},
  language     = {eng},
  number       = {2},
  pages        = {97--104},
  publisher    = {Bentham Science Publishers},
  series       = {Endocrine, Metabolic & Immune Disorders - Drug Targets},
  title        = {S100A9 as a pharmacological target molecule in inflammation and cancer.},
  volume       = {15},
  year         = {2015},
}