Transplantation and Inflammation: implications for the modification of chemokine function

Barker, Catriona E., Ali, Simi, O'Boyle, Graeme and Kirby, John A. (2014) Transplantation and Inflammation: implications for the modification of chemokine function. Immunology, 143 (138-14). ISSN 1365-2567

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Abstract

Oxidative stress is a major and recurring cause of damage during inflammation, especially
following organ transplantation. Initial ischaemia-reperfusion injury causes the production of
many reactive oxygen and nitrogen species,
and subsequent recruitment and activation of
inflammatory cells can lead to further oxidative stress. This stress is well known to cause
damage at the cellular level, for example by induction of senescence leading to the production
of a characteristic senescence associated secretory phenotype (SASP). Chemokines are an
important component of the SASP, recruiting further leukocytes and reinforcing the stress and
senescence responses. As well as inducing the
production of proteins, including chemokines,
oxidative stress can alter proteins themselves, both directly and by induction of enzymes
capable of modification. These alterations can lead to important modifications to their
biological activity and also alter detection
by some antibodies, potentially limiting the
biological relevance of some immunochemical and proteomic biomarkers. Peroxynitrite, a
reactive nitrogen species generated during inflammation and ischaemia, can cause such
modifications by nitrating chemokines. Matrix metalloproteinases, released by many stressed
cells, can cleave chemokines, altering function, whilst peptidylarginine deiminases can
inactivate certain chemokines by citrullination. This review discusses the relationship between
inflammation and post-translational modification, focussing on the functional modulation of
transplant-relevant pro-inflammatory chemokines.

Item Type: Article
Uncontrolled Keywords: Chemokines; post-translational modification; inflammation; stress
Subjects: Sciences > Health Sciences
Divisions: Faculty of Applied Sciences
Faculty of Applied Sciences > Department of Pharmacy Health and Wellbeing
Health Sciences and Wellbeing Beacon
Depositing User: Hannah Dodd
Date Deposited: 16 Jul 2014 14:19
Last Modified: 03 Jun 2015 10:30
URI: http://sure.sunderland.ac.uk/id/eprint/5017

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