Geranylgeranyl transferase regulates streptococcal m1 protein-induced CXC chemokine formation and neutrophil recruitment in the lung.
Zhang, Songen LU ; Rahman, Milladur LU
; Jeppsson, Bengt
LU
; Herwald, Heiko
LU
and Thorlacius, Henrik
LU
(2013)
In Shock
39(3).
p.293-298
- Abstract
- ABSTRACT: Streptococcal toxic shock syndrome is most frequently associated with Streptococcus pyogenes of the M1 serotype. Simvastatin protects against M1 protein-induced acute lung damage, although downstream mechanisms remain elusive. Herein, we hypothesized that geranylgeranylation might regulate proinflammatory effects in M1 protein-induced lung injury. Male C57BL/6 mice received the geranylgeranyl transferase inhibitor, GGTI-2133, before M1 protein injection. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema, and CXC chemokine formation. Mac-1 expression on neutrophils was quantified by use of flow cytometry. Quantitative reverse transcriptase-polymerase chain reaction was used to... (More)
- ABSTRACT: Streptococcal toxic shock syndrome is most frequently associated with Streptococcus pyogenes of the M1 serotype. Simvastatin protects against M1 protein-induced acute lung damage, although downstream mechanisms remain elusive. Herein, we hypothesized that geranylgeranylation might regulate proinflammatory effects in M1 protein-induced lung injury. Male C57BL/6 mice received the geranylgeranyl transferase inhibitor, GGTI-2133, before M1 protein injection. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema, and CXC chemokine formation. Mac-1 expression on neutrophils was quantified by use of flow cytometry. Quantitative reverse transcriptase-polymerase chain reaction was used to determine gene expression of CXC chemokines in alveolar macrophages. GGTI-2133 reduced M1 protein-provoked infiltration of neutrophils, edema, and tissue injury in the lung. Inhibition of geranylgeranyl transferase had no effect on M1 protein-evoked upregulation of Mac-1 on neutrophils. However, geranylgeranyl transferase inhibition completely inhibited pulmonary formation of CXC chemokines in mice exposed to M1 protein. Notably, GGTI-2133 abolished M1 protein-induced gene expression of CXC chemokines in alveolar macrophages. These novel findings indicate that geranylgeranyl transferase is an important regulator of neutrophil recruitment and CXC chemokine production in the lung. Thus, targeting geranylgeranyl transferase might be a potent way to ameliorate streptococcal M1 protein-triggered acute lung injury. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3560432
- author
- Zhang, Songen
LU
; Rahman, Milladur
LU
; Jeppsson, Bengt
LU
; Herwald, Heiko
LU
and Thorlacius, Henrik
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Shock
- volume
- 39
- issue
- 3
- pages
- 293 - 298
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000315186100010
- pmid:23364431
- scopus:84874264150
- pmid:23364431
- ISSN
- 1540-0514
- DOI
- 10.1097/SHK.0b013e3182844523
- language
- English
- LU publication?
- yes
- id
- a1e86335-f2c7-4375-af97-212013d89081 (old id 3560432)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23364431?dopt=Abstract
- date added to LUP
- 2016-04-01 09:56:52
- date last changed
- 2022-02-24 20:52:35
@article{a1e86335-f2c7-4375-af97-212013d89081,
abstract = {{ABSTRACT: Streptococcal toxic shock syndrome is most frequently associated with Streptococcus pyogenes of the M1 serotype. Simvastatin protects against M1 protein-induced acute lung damage, although downstream mechanisms remain elusive. Herein, we hypothesized that geranylgeranylation might regulate proinflammatory effects in M1 protein-induced lung injury. Male C57BL/6 mice received the geranylgeranyl transferase inhibitor, GGTI-2133, before M1 protein injection. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema, and CXC chemokine formation. Mac-1 expression on neutrophils was quantified by use of flow cytometry. Quantitative reverse transcriptase-polymerase chain reaction was used to determine gene expression of CXC chemokines in alveolar macrophages. GGTI-2133 reduced M1 protein-provoked infiltration of neutrophils, edema, and tissue injury in the lung. Inhibition of geranylgeranyl transferase had no effect on M1 protein-evoked upregulation of Mac-1 on neutrophils. However, geranylgeranyl transferase inhibition completely inhibited pulmonary formation of CXC chemokines in mice exposed to M1 protein. Notably, GGTI-2133 abolished M1 protein-induced gene expression of CXC chemokines in alveolar macrophages. These novel findings indicate that geranylgeranyl transferase is an important regulator of neutrophil recruitment and CXC chemokine production in the lung. Thus, targeting geranylgeranyl transferase might be a potent way to ameliorate streptococcal M1 protein-triggered acute lung injury.}},
author = {{Zhang, Songen and Rahman, Milladur and Jeppsson, Bengt and Herwald, Heiko and Thorlacius, Henrik}},
issn = {{1540-0514}},
language = {{eng}},
number = {{3}},
pages = {{293--298}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Shock}},
title = {{Geranylgeranyl transferase regulates streptococcal m1 protein-induced CXC chemokine formation and neutrophil recruitment in the lung.}},
url = {{http://dx.doi.org/10.1097/SHK.0b013e3182844523}},
doi = {{10.1097/SHK.0b013e3182844523}},
volume = {{39}},
year = {{2013}},
}