Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps

Robert D Gray; Christopher Lucas; Annie Mackellar; Feng Li; Katia Hiersemenzel; Chris Haslett; Donald J Davidson; Adriano G Rossi

doi:10.1186/1476-9255-10-12

Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps

Robert D Gray, Christopher Lucas, Annie Mackellar, Feng Li, Katia Hiersemenzel, Chris Haslett, Donald J Davidson, Adriano G Rossi

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

BACKGROUND: Activation of NADPH oxidase is required for neutrophil extracellular trap (NET) formation. Protein kinase C (PKC) is an upstream mediator of NADPH oxidase activation and thus likely to have a role in NET formation.

METHODS: Pharmacological inhibitors were used to block PKC activity in neutrophils harvested from healthy donor blood.

RESULTS: Pan PKC inhibition with Ro-31-8220 (p<0.001), conventional PKC inhibition with Go 6976 (p<0.001) and specific PKCβ inhibition with LY333531 (p<0.01) blocked NET formation in response to PMA. Inhibition of novel and atypical PKC had no effect. LY333531 blocked NET induction by the diacylglycerol analogue OAG (conventional PKC activator) (p<0.001).

CONCLUSIONS: Conventional PKCs have a prominent role in NET formation. Furthermore PKCβ is the major isoform implicated in NET formation.

Original language	English
Article number	12
Number of pages	8
Journal	Journal of inflammation
Volume	10
Issue number	1
DOIs	https://doi.org/10.1186/1476-9255-10-12
Publication status	Published - 21 Mar 2013

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10.1186/1476-9255-10-12

Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps
© 2013 Gray et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Final published version, 663 KBLicence: Creative Commons: Attribution (CC-BY)

http://www.journal-inflammation.com/content/10/1/12

The role of cyclin-dependent kinase-9 inhibition in promoting the resolution of chronic inflammation
Rossi, A. & Haslett, C.
MRC
1/05/13 → 30/10/19
Project: Research
PhD STUDENT - JOANNE SIMPSON - Supervisor MOHINI GRAY
Iredale, J.
MRC
1/09/12 → 31/08/16
Project: Research
Cathelicidins as immunomodulators of host defence against infectious diseases
Davidson, D.
MRC
1/04/11 → 31/03/17
Project: Research

Cite this

@article{99b94f6cfc5e41f09488cd1426261f43,

title = "Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps",

abstract = "BACKGROUND: Activation of NADPH oxidase is required for neutrophil extracellular trap (NET) formation. Protein kinase C (PKC) is an upstream mediator of NADPH oxidase activation and thus likely to have a role in NET formation.METHODS: Pharmacological inhibitors were used to block PKC activity in neutrophils harvested from healthy donor blood.RESULTS: Pan PKC inhibition with Ro-31-8220 (p<0.001), conventional PKC inhibition with Go 6976 (p<0.001) and specific PKCβ inhibition with LY333531 (p<0.01) blocked NET formation in response to PMA. Inhibition of novel and atypical PKC had no effect. LY333531 blocked NET induction by the diacylglycerol analogue OAG (conventional PKC activator) (p<0.001).CONCLUSIONS: Conventional PKCs have a prominent role in NET formation. Furthermore PKCβ is the major isoform implicated in NET formation.",

author = "Gray, {Robert D} and Christopher Lucas and Annie Mackellar and Feng Li and Katia Hiersemenzel and Chris Haslett and Davidson, {Donald J} and Rossi, {Adriano G}",

note = "RDG is a Wellcome Trust Fellow (093767). DD is an MRC Senior Research Fellow (G1002046). This work was also funded by the Wellcome Trust (WT094415; CL) and the MRC (G0601481; AGR and CH). ",

year = "2013",

month = mar,

day = "21",

doi = "10.1186/1476-9255-10-12",

language = "English",

volume = "10",

journal = "Journal of inflammation",

issn = "1476-9255",

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TY - JOUR

T1 - Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps

AU - Gray, Robert D

AU - Lucas, Christopher

AU - Mackellar, Annie

AU - Li, Feng

AU - Hiersemenzel, Katia

AU - Haslett, Chris

AU - Davidson, Donald J

AU - Rossi, Adriano G

N1 - RDG is a Wellcome Trust Fellow (093767). DD is an MRC Senior Research Fellow (G1002046). This work was also funded by the Wellcome Trust (WT094415; CL) and the MRC (G0601481; AGR and CH).

PY - 2013/3/21

Y1 - 2013/3/21

N2 - BACKGROUND: Activation of NADPH oxidase is required for neutrophil extracellular trap (NET) formation. Protein kinase C (PKC) is an upstream mediator of NADPH oxidase activation and thus likely to have a role in NET formation.METHODS: Pharmacological inhibitors were used to block PKC activity in neutrophils harvested from healthy donor blood.RESULTS: Pan PKC inhibition with Ro-31-8220 (p<0.001), conventional PKC inhibition with Go 6976 (p<0.001) and specific PKCβ inhibition with LY333531 (p<0.01) blocked NET formation in response to PMA. Inhibition of novel and atypical PKC had no effect. LY333531 blocked NET induction by the diacylglycerol analogue OAG (conventional PKC activator) (p<0.001).CONCLUSIONS: Conventional PKCs have a prominent role in NET formation. Furthermore PKCβ is the major isoform implicated in NET formation.

AB - BACKGROUND: Activation of NADPH oxidase is required for neutrophil extracellular trap (NET) formation. Protein kinase C (PKC) is an upstream mediator of NADPH oxidase activation and thus likely to have a role in NET formation.METHODS: Pharmacological inhibitors were used to block PKC activity in neutrophils harvested from healthy donor blood.RESULTS: Pan PKC inhibition with Ro-31-8220 (p<0.001), conventional PKC inhibition with Go 6976 (p<0.001) and specific PKCβ inhibition with LY333531 (p<0.01) blocked NET formation in response to PMA. Inhibition of novel and atypical PKC had no effect. LY333531 blocked NET induction by the diacylglycerol analogue OAG (conventional PKC activator) (p<0.001).CONCLUSIONS: Conventional PKCs have a prominent role in NET formation. Furthermore PKCβ is the major isoform implicated in NET formation.

U2 - 10.1186/1476-9255-10-12

DO - 10.1186/1476-9255-10-12

M3 - Article

C2 - 23514610

SN - 1476-9255

VL - 10

JO - Journal of inflammation

JF - Journal of inflammation

IS - 1

M1 - 12

ER -

Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps

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Projects

The role of cyclin-dependent kinase-9 inhibition in promoting the resolution of chronic inflammation

PhD STUDENT - JOANNE SIMPSON - Supervisor MOHINI GRAY

Cathelicidins as immunomodulators of host defence against infectious diseases

Cite this