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Matrix metalloproteinases and tissue damage in HIV-tuberculosis immune reconstitution inflammatory syndrome

Matrix metalloproteinases and tissue damage in HIV-tuberculosis immune reconstitution inflammatory syndrome
Matrix metalloproteinases and tissue damage in HIV-tuberculosis immune reconstitution inflammatory syndrome
The HIV-TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) can complicate combined treatments for HIV-1 and TB. Little is known about tissue damage in TB-IRIS. Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix and consequently may play a role in such immunopathology. Here we investigated the involvement of MMPs in TB-IRIS. We determined MMP transcript abundance and secreted protein in Mycobacterium tuberculosis stimulated PBMCs from 22 TB-IRIS patients and 22 non-IRIS controls. We also measured MMP protein levels in corresponding serum and the effect of prednisone — which reduces the duration of symptoms in IRIS patients — or placebo treatment on MMP transcript and circulating MMP protein levels. PBMCs from TB-IRIS had increased MMP-1, -3, -7, and -10 transcript levels when compared with those of controls at either 6 or 24 h. Similarly, MMP-1, -3, -7, and -10 protein secretion in stimulated cultures was higher in TB-IRIS than in controls. Serum MMP-7 concentration was elevated in TB-IRIS and 2 weeks of corticosteroid therapy decreased this level, although not significantly. TB-IRIS is associated with a distinct pattern of MMP gene and protein activation. Modulation of dysregulated MMP activity may represent a novel therapeutic approach to alleviate TB-IRIS in HIV-TB patients undergoing treatment
0014-2980
127-136
Tadokera, R.
c95fd08a-3888-42f9-aa9b-cc5c60ec364d
Meintjes, G.A.
57556156-c55f-4333-85eb-e67c90e5ae99
Wilkinson, K.A.
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Skolimowska, K.H.
b6c03b46-e511-4fac-8ec1-4f13c8787655
Walker, N.
09eb6162-d2d8-4ce5-9334-26c39966bb04
Friedland, J.S.
e64a7af8-b969-4426-82e6-5ebe819799c9
Maartens, G.
d1c80472-bab4-47cd-a27c-42ee43a24e15
Elkington, P.T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Wilkinson, R.J.
d08be0b9-dbe4-46c5-9297-68733a4e2f9f
Tadokera, R.
c95fd08a-3888-42f9-aa9b-cc5c60ec364d
Meintjes, G.A.
57556156-c55f-4333-85eb-e67c90e5ae99
Wilkinson, K.A.
85c0acc3-9f8f-409b-a580-d7ae715ce21c
Skolimowska, K.H.
b6c03b46-e511-4fac-8ec1-4f13c8787655
Walker, N.
09eb6162-d2d8-4ce5-9334-26c39966bb04
Friedland, J.S.
e64a7af8-b969-4426-82e6-5ebe819799c9
Maartens, G.
d1c80472-bab4-47cd-a27c-42ee43a24e15
Elkington, P.T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Wilkinson, R.J.
d08be0b9-dbe4-46c5-9297-68733a4e2f9f

Tadokera, R., Meintjes, G.A., Wilkinson, K.A., Skolimowska, K.H., Walker, N., Friedland, J.S., Maartens, G., Elkington, P.T. and Wilkinson, R.J. (2014) Matrix metalloproteinases and tissue damage in HIV-tuberculosis immune reconstitution inflammatory syndrome. European Journal of Immunology, 44 (1), 127-136. (doi:10.1002/eji.201343593). (PMID:24136296)

Record type: Article

Abstract

The HIV-TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) can complicate combined treatments for HIV-1 and TB. Little is known about tissue damage in TB-IRIS. Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix and consequently may play a role in such immunopathology. Here we investigated the involvement of MMPs in TB-IRIS. We determined MMP transcript abundance and secreted protein in Mycobacterium tuberculosis stimulated PBMCs from 22 TB-IRIS patients and 22 non-IRIS controls. We also measured MMP protein levels in corresponding serum and the effect of prednisone — which reduces the duration of symptoms in IRIS patients — or placebo treatment on MMP transcript and circulating MMP protein levels. PBMCs from TB-IRIS had increased MMP-1, -3, -7, and -10 transcript levels when compared with those of controls at either 6 or 24 h. Similarly, MMP-1, -3, -7, and -10 protein secretion in stimulated cultures was higher in TB-IRIS than in controls. Serum MMP-7 concentration was elevated in TB-IRIS and 2 weeks of corticosteroid therapy decreased this level, although not significantly. TB-IRIS is associated with a distinct pattern of MMP gene and protein activation. Modulation of dysregulated MMP activity may represent a novel therapeutic approach to alleviate TB-IRIS in HIV-TB patients undergoing treatment

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Accepted/In Press date: 25 September 2013
e-pub ahead of print date: 18 October 2013
Published date: January 2014
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 359632
URI: https://eprints.soton.ac.uk/id/eprint/359632
ISSN: 0014-2980
PURE UUID: 9dc010c8-d73b-4782-b5f6-0e17eadfa571
ORCID for P.T. Elkington: ORCID iD orcid.org/0000-0003-0390-0613

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Date deposited: 08 Nov 2013 09:13
Last modified: 10 Sep 2019 00:37

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