Enhanced Systemic Response of Matrix Metalloproteinases and Their Regulators in Campylobacter and Salmonella Patients.

Anna Nilsson,David Lennebratt,Hilpi Rautelin,Anders Lannergård,Timo Sorsa,Taina Tervahartiala

doi:10.3390/diagnostics8040082

Anna Nilsson, David Lennebratt + Show 4 more

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https://doi.org/10.3390/diagnostics8040082

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Abstract

Campylobacters are major enteropathogens worldwide with a substantial financial burden. Matrix metalloproteinases (MMPs) are proteolytic metalloendopeptidases with ability to modify immune response and shown to be upregulated in patients with several tissue destructive diseases, including infections. We measured here serum concentrations of MMP-8 and MMP-9 together with their regulators myeloperoxidase (MPO), human neutrophil elastase (HNE), and tissue inhibitor of metalloproteinases (TIMP)-1 in 80 Campylobacter and 25 Salmonella patients as well as in 27 healthy controls. Paired serum samples were available for 73 and 23 patients, respectively. When the initial serum samples were compared to those from controls, both Campylobacter and Salmonella patients showed elevated concentrations of all biomarkers tested (p ≤ 0.037). In the follow-up samples, collected about 25 days afterwards, MMP-8 levels of Campylobacter patients had already turned to normal but all the other biomarkers still showed elevated, although from the initial levels significantly dropped, levels. For the follow-up samples of Salmonella patients, only MMP-9 and MPO levels were at a significantly higher level than in controls. It remains to be studied if the systematically enhanced neutrophil-derived proteolytic and oxidative stress, induced by Campylobacter infection as shown here and persisting for several weeks, is important for the development of late sequelae.

Highlights

Campylobacter is the most common cause of bacterial gastroenteritis in most parts of the world and the financial burden of the infections in the European Union alone is estimated to be 2.4 billion euro every year [1,2]
Matrix metalloproteinases (MMPs) are regulated at different levels; transcription and secretion, activation of the proenzyme, and local activity of MMP are regulated by tissue inhibitors of metalloproteinases (TIMPs) [9,11]
Degranulation of neutrophils releases human neutrophil elastase (HNE), which is a serine protease involved in host response to bacteria and can activate latent proMMPs and inactivate their endogenous inhibitors, TIMPs [10]

Summary

Introduction

Campylobacter is the most common cause of bacterial gastroenteritis in most parts of the world and the financial burden of the infections in the European Union alone is estimated to be 2.4 billion euro every year [1,2]. The proenzymes are locally activated and involved in leucocyte recruitment to the inflammation site [10]. MMPs are regulated at different levels; transcription and secretion, activation of the proenzyme, and local activity of MMP are regulated by tissue inhibitors of metalloproteinases (TIMPs) [9,11]. MPO can, by generating oxidants, activate MMPs and inactivate TIMPs [10,12]. Degranulation of neutrophils releases human neutrophil elastase (HNE), which is a serine protease involved in host response to bacteria and can activate latent proMMPs and inactivate their endogenous inhibitors, TIMPs [10]

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