Publication

Identification of Highly Connected Hub Genes in the Protective Response Program of Human Macrophages and Microglia Activated by Alpha B-Crystallin

Holtman, I. R., Bsibsi, M., Gerritsen, W. H., Boddeke, H. W. G. M., Eggen, B. J. L., van der Valk, P., Kipp, M., van Noort, J. M. & Amor, S., Mar-2017, In : Glia. 65, 3, p. 460-473 14 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Holtman, I. R., Bsibsi, M., Gerritsen, W. H., Boddeke, H. W. G. M., Eggen, B. J. L., van der Valk, P., ... Amor, S. (2017). Identification of Highly Connected Hub Genes in the Protective Response Program of Human Macrophages and Microglia Activated by Alpha B-Crystallin. Glia, 65(3), 460-473. https://doi.org/10.1002/glia.23104

Author

Holtman, Inge R. ; Bsibsi, Malika ; Gerritsen, Wouter H. ; Boddeke, Hendrikus W. G. M. ; Eggen, Bart J. L. ; van der Valk, Paul ; Kipp, Markus ; van Noort, Johannes M. ; Amor, Sandra. / Identification of Highly Connected Hub Genes in the Protective Response Program of Human Macrophages and Microglia Activated by Alpha B-Crystallin. In: Glia. 2017 ; Vol. 65, No. 3. pp. 460-473.

Harvard

Holtman, IR, Bsibsi, M, Gerritsen, WH, Boddeke, HWGM, Eggen, BJL, van der Valk, P, Kipp, M, van Noort, JM & Amor, S 2017, 'Identification of Highly Connected Hub Genes in the Protective Response Program of Human Macrophages and Microglia Activated by Alpha B-Crystallin', Glia, vol. 65, no. 3, pp. 460-473. https://doi.org/10.1002/glia.23104

Standard

Identification of Highly Connected Hub Genes in the Protective Response Program of Human Macrophages and Microglia Activated by Alpha B-Crystallin. / Holtman, Inge R.; Bsibsi, Malika; Gerritsen, Wouter H.; Boddeke, Hendrikus W. G. M.; Eggen, Bart J. L.; van der Valk, Paul; Kipp, Markus; van Noort, Johannes M.; Amor, Sandra.

In: Glia, Vol. 65, No. 3, 03.2017, p. 460-473.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Holtman IR, Bsibsi M, Gerritsen WH, Boddeke HWGM, Eggen BJL, van der Valk P et al. Identification of Highly Connected Hub Genes in the Protective Response Program of Human Macrophages and Microglia Activated by Alpha B-Crystallin. Glia. 2017 Mar;65(3):460-473. https://doi.org/10.1002/glia.23104


BibTeX

@article{83ba956ebeea4618b9c2ad0c260945e0,
title = "Identification of Highly Connected Hub Genes in the Protective Response Program of Human Macrophages and Microglia Activated by Alpha B-Crystallin",
abstract = "The glial stress protein alpha B-crystallin (HSPB5) is an endogenous agonist for Toll-like receptor 2 in CD14 1 cells. Following systemic administration, HSPB5 acts as a potent inhibitor of neuroinflammation in animal models and reduces lesion development in multiple sclerosis patients. Here, we show that systemically administered HSPB5 rapidly crosses the blood-brain barrier, implicating microglia as additional targets for HSPB5 along with peripheral monocytes and macrophages. To compare key players in the HSPB5-induced protective response of human macrophages and microglia, we applied weighted gene co-expression network analysis on transcript expression data obtained 1 and 4 h after activation. This approach identified networks of genes that are co-expressed in all datasets, thus reducing the complexity of the nonsynchronous waves of transcripts that appear after activation by HSPB5. In both cell types, HSPB5 activates a network of highly connected genes that appear to be functionally equivalent and consistent with the therapeutic effects of HSPB5 in vivo, since both networks include factors that suppress apoptosis, the production of proinflammatory factors, and the development of adaptive immunity. Yet, hub genes at the core of the network in either cell type were strikingly different. They prominently feature the well-known tolerance-promoting programmeddeath ligand 1 as a key player in the macrophage response to HSPB5, and the immune-regulatory enzyme cyclooxygenase-2 (COX-2) in that of microglia. This latter finding indicates that despite its reputation as a potential target for nonsteroidal antiinflammatory drugs, microglial COX-2 plays a central role in the therapeutic effects of HSPB5 during neuroinflammation.",
keywords = "HSPB5, TLR2, microglia, alternative activation, COX-2, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, MULTIPLE-SCLEROSIS LESIONS, IMMUNE-RESPONSE, BRAIN-INJURY, CELLS, NEUROINFLAMMATION, CYCLOOXYGENASE-2, NETWORK, INTERLEUKIN-15, INFLAMMATION",
author = "Holtman, {Inge R.} and Malika Bsibsi and Gerritsen, {Wouter H.} and Boddeke, {Hendrikus W. G. M.} and Eggen, {Bart J. L.} and {van der Valk}, Paul and Markus Kipp and {van Noort}, {Johannes M.} and Sandra Amor",
year = "2017",
month = "3",
doi = "10.1002/glia.23104",
language = "English",
volume = "65",
pages = "460--473",
journal = "Glia",
issn = "0894-1491",
publisher = "Wiley",
number = "3",

}

RIS

TY - JOUR

T1 - Identification of Highly Connected Hub Genes in the Protective Response Program of Human Macrophages and Microglia Activated by Alpha B-Crystallin

AU - Holtman, Inge R.

AU - Bsibsi, Malika

AU - Gerritsen, Wouter H.

AU - Boddeke, Hendrikus W. G. M.

AU - Eggen, Bart J. L.

AU - van der Valk, Paul

AU - Kipp, Markus

AU - van Noort, Johannes M.

AU - Amor, Sandra

PY - 2017/3

Y1 - 2017/3

N2 - The glial stress protein alpha B-crystallin (HSPB5) is an endogenous agonist for Toll-like receptor 2 in CD14 1 cells. Following systemic administration, HSPB5 acts as a potent inhibitor of neuroinflammation in animal models and reduces lesion development in multiple sclerosis patients. Here, we show that systemically administered HSPB5 rapidly crosses the blood-brain barrier, implicating microglia as additional targets for HSPB5 along with peripheral monocytes and macrophages. To compare key players in the HSPB5-induced protective response of human macrophages and microglia, we applied weighted gene co-expression network analysis on transcript expression data obtained 1 and 4 h after activation. This approach identified networks of genes that are co-expressed in all datasets, thus reducing the complexity of the nonsynchronous waves of transcripts that appear after activation by HSPB5. In both cell types, HSPB5 activates a network of highly connected genes that appear to be functionally equivalent and consistent with the therapeutic effects of HSPB5 in vivo, since both networks include factors that suppress apoptosis, the production of proinflammatory factors, and the development of adaptive immunity. Yet, hub genes at the core of the network in either cell type were strikingly different. They prominently feature the well-known tolerance-promoting programmeddeath ligand 1 as a key player in the macrophage response to HSPB5, and the immune-regulatory enzyme cyclooxygenase-2 (COX-2) in that of microglia. This latter finding indicates that despite its reputation as a potential target for nonsteroidal antiinflammatory drugs, microglial COX-2 plays a central role in the therapeutic effects of HSPB5 during neuroinflammation.

AB - The glial stress protein alpha B-crystallin (HSPB5) is an endogenous agonist for Toll-like receptor 2 in CD14 1 cells. Following systemic administration, HSPB5 acts as a potent inhibitor of neuroinflammation in animal models and reduces lesion development in multiple sclerosis patients. Here, we show that systemically administered HSPB5 rapidly crosses the blood-brain barrier, implicating microglia as additional targets for HSPB5 along with peripheral monocytes and macrophages. To compare key players in the HSPB5-induced protective response of human macrophages and microglia, we applied weighted gene co-expression network analysis on transcript expression data obtained 1 and 4 h after activation. This approach identified networks of genes that are co-expressed in all datasets, thus reducing the complexity of the nonsynchronous waves of transcripts that appear after activation by HSPB5. In both cell types, HSPB5 activates a network of highly connected genes that appear to be functionally equivalent and consistent with the therapeutic effects of HSPB5 in vivo, since both networks include factors that suppress apoptosis, the production of proinflammatory factors, and the development of adaptive immunity. Yet, hub genes at the core of the network in either cell type were strikingly different. They prominently feature the well-known tolerance-promoting programmeddeath ligand 1 as a key player in the macrophage response to HSPB5, and the immune-regulatory enzyme cyclooxygenase-2 (COX-2) in that of microglia. This latter finding indicates that despite its reputation as a potential target for nonsteroidal antiinflammatory drugs, microglial COX-2 plays a central role in the therapeutic effects of HSPB5 during neuroinflammation.

KW - HSPB5

KW - TLR2

KW - microglia

KW - alternative activation

KW - COX-2

KW - EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

KW - MULTIPLE-SCLEROSIS LESIONS

KW - IMMUNE-RESPONSE

KW - BRAIN-INJURY

KW - CELLS

KW - NEUROINFLAMMATION

KW - CYCLOOXYGENASE-2

KW - NETWORK

KW - INTERLEUKIN-15

KW - INFLAMMATION

U2 - 10.1002/glia.23104

DO - 10.1002/glia.23104

M3 - Article

VL - 65

SP - 460

EP - 473

JO - Glia

JF - Glia

SN - 0894-1491

IS - 3

ER -

ID: 44606109