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C-36 peptide, a degradation product of alpha1-antitrypsin, modulates human monocyte activation through LPS signaling pathways.

Subramaniyam, Devipriya LU ; Glader, Pernilla LU ; von Wachenfeldt, Karin ; Burneckiene, Jurate ; Stevens, Tim and Janciauskiene, Sabina LU (2006) In International Journal of Biochemistry & Cell Biology 38(4). p.563-575
Abstract
alpha 1-Antitrypsin (AAT), a major endogenous inhibitor of serine proteases, plays an important role in minimizing proteolytic injury to host tissue at sites of infection and inflammation. There is now increasing evidence that AAT undergoes post-translational modifications to yield by-products With novel biological activity. One Such molecule, the C-terminal fragment of AAT, corresponding to residues 359-394 (C-36 peptide) has been reported to stimulate significant pro-inflammatory activity in monocytes and neutrophils in vitro. In this study we showed that C-36 peptide is present in human lung tissue and mimics the effects of lipopolysaccharide (LIPS), albeit with lower magnitude, by inducing monocyte cytokine (TNF alpha, IL-I beta) and... (More)
alpha 1-Antitrypsin (AAT), a major endogenous inhibitor of serine proteases, plays an important role in minimizing proteolytic injury to host tissue at sites of infection and inflammation. There is now increasing evidence that AAT undergoes post-translational modifications to yield by-products With novel biological activity. One Such molecule, the C-terminal fragment of AAT, corresponding to residues 359-394 (C-36 peptide) has been reported to stimulate significant pro-inflammatory activity in monocytes and neutrophils in vitro. In this study we showed that C-36 peptide is present in human lung tissue and mimics the effects of lipopolysaccharide (LIPS), albeit with lower magnitude, by inducing monocyte cytokine (TNF alpha, IL-I beta) and chemokine (IL-8) release in conjunction with the activation of nuclear factor-kappa B (NF-kappa B). Using receptor blocking antibodies and protein kinase inhibitors, we further demonstrated that C-36, like LPS, utilizes CD14 and Toll-like receptor 4 (TLR4) receptors and enzymes of the mitogen-activated protein kinase (MAPK) signaling pathways to stimulate monocyte TNF alpha release. The specificity of C-36 effects were demonstrated by failure of a shorter peptide (C-20) to elicit biological activity and the failure of C-36 to inhibit M/CD28-stimulated IL-2 receptor expression or proliferation in T-cells which lack TLR4 and CD14. We suggest that C-36 mediates its effects though the activation of LPS signaling pathways. (c) 2005 Elsevier Ltd. All rights reserved. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alpha 1-antitrypsin, C-36 peptide of alpha 1-antitrypsin, monocytes, endotoxin, lipopolysaccharide
in
International Journal of Biochemistry & Cell Biology
volume
38
issue
4
pages
563 - 575
publisher
Elsevier
external identifiers
  • wos:000235705100009
  • pmid:16384723
  • scopus:30944435267
  • pmid:16384723
ISSN
1878-5875
DOI
10.1016/j.biocel.2005.09.021
language
English
LU publication?
yes
id
70ddfdea-5ffc-4032-a499-bf19cab45e1a (old id 148435)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16384723&dopt=Abstract
date added to LUP
2016-04-01 16:57:00
date last changed
2021-08-18 01:06:25
@article{70ddfdea-5ffc-4032-a499-bf19cab45e1a,
  abstract     = {alpha 1-Antitrypsin (AAT), a major endogenous inhibitor of serine proteases, plays an important role in minimizing proteolytic injury to host tissue at sites of infection and inflammation. There is now increasing evidence that AAT undergoes post-translational modifications to yield by-products With novel biological activity. One Such molecule, the C-terminal fragment of AAT, corresponding to residues 359-394 (C-36 peptide) has been reported to stimulate significant pro-inflammatory activity in monocytes and neutrophils in vitro. In this study we showed that C-36 peptide is present in human lung tissue and mimics the effects of lipopolysaccharide (LIPS), albeit with lower magnitude, by inducing monocyte cytokine (TNF alpha, IL-I beta) and chemokine (IL-8) release in conjunction with the activation of nuclear factor-kappa B (NF-kappa B). Using receptor blocking antibodies and protein kinase inhibitors, we further demonstrated that C-36, like LPS, utilizes CD14 and Toll-like receptor 4 (TLR4) receptors and enzymes of the mitogen-activated protein kinase (MAPK) signaling pathways to stimulate monocyte TNF alpha release. The specificity of C-36 effects were demonstrated by failure of a shorter peptide (C-20) to elicit biological activity and the failure of C-36 to inhibit M/CD28-stimulated IL-2 receptor expression or proliferation in T-cells which lack TLR4 and CD14. We suggest that C-36 mediates its effects though the activation of LPS signaling pathways. (c) 2005 Elsevier Ltd. All rights reserved.},
  author       = {Subramaniyam, Devipriya and Glader, Pernilla and von Wachenfeldt, Karin and Burneckiene, Jurate and Stevens, Tim and Janciauskiene, Sabina},
  issn         = {1878-5875},
  language     = {eng},
  number       = {4},
  pages        = {563--575},
  publisher    = {Elsevier},
  series       = {International Journal of Biochemistry & Cell Biology},
  title        = {C-36 peptide, a degradation product of alpha1-antitrypsin, modulates human monocyte activation through LPS signaling pathways.},
  url          = {http://dx.doi.org/10.1016/j.biocel.2005.09.021},
  doi          = {10.1016/j.biocel.2005.09.021},
  volume       = {38},
  year         = {2006},
}