Inhibition of NLRP3 inflammasome contributes to protective effect of 5,14-HEDGE against lipopolysaccharide-induced septic shock

Bahar Tunctan, Sefika Pinar Kucukkavruk, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat, Mahesh Paudyal, J R Falck, Kafait Ullah Malik

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background and Objective: Nucleotide binding domain and leucine-rich repeat protein 3 (NLRP3) is reported to be involved in the pathogenesis of numerous inflammatory diseases including Alzheimer disease, Parkinson disease, Prion disease and type 2 diabetes mellitus. Previous studies have demonstrated that a stable synthetic analog of 20-hydroxyeicosatetraenoic acid (20-HETE), N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE), prevents vascular hyporeactivity, hypotension, tachycardia, inflammation and mortality in a rodent model of septic shock. This study was aimed to assess effect of 5,14-HEDGE on the changes in NLRP3/apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)/pro-caspase-1 inflammasome in lipopolysaccharide (LPS)-induced septic shock in rats. Methodology: Rats were injected with saline (4 mL kg-1) or LPS (10 mg kg-1) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. 5,14-HEDGE (30 mg kg-1) was administered to rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and kidney, heart, thoracic aorta and superior mesenteric artery were isolated for measurement of caspase-1/11 p20, NLRP3, ASC and β-actin proteins as well as interleukin-1β (IL-1β) levels. Data were analysed by one-way ANOVA followed by Student-Newman-Keuls test for multiple comparisons, Kruskal-Wallis test followed by Dunns test for multiple comparisons and Student's test or Mann-Whitney U tests when appropriate. Results: Blood pressure decreased by 33 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. In the LPS-treated rats, tissue protein expression of caspase-1/11 p20, NLRP3 and ASC in addition to IL-1β levels were increased. The 5,14-HEDGE prevented the LPS-induced changes. Conclusion: These findings suggest that inhibition of renal, cardiac and vascular formation/activity of NLRP3/ASC/pro-caspase-1 inflammasome involves in the protective effect of 5,14-HEDGE on LPS-induced septic shock in rats.

Original languageEnglish (US)
Pages (from-to)654-666
Number of pages13
JournalInternational Journal of Pharmacology
Volume13
Issue number6
DOIs
StatePublished - 2017

Fingerprint

Inflammasomes
Septic Shock
Lipopolysaccharides
Caspase 1
Interleukin-1
Heart Rate
Students
Blood Pressure
Kidney
Injections
Proteins
Prion Diseases
Superior Mesenteric Artery
Inhibition (Psychology)
N-(20-hydroxyeicosa-5,14-dienoyl)glycine
Nonparametric Statistics
Thoracic Aorta
Tachycardia
Hypotension
Type 2 Diabetes Mellitus

Keywords

  • 14-HEDGE
  • 20-HETE
  • 5
  • Blood pressure
  • Heart rate
  • IL-1β
  • Inflammation
  • Lipopolysaccharide
  • NLRP3 inflammasome

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tunctan, B., Kucukkavruk, S. P., Temiz-Resitoglu, M., Guden, D. S., Sari, A. N., Sahan-Firat, S., ... Malik, K. U. (2017). Inhibition of NLRP3 inflammasome contributes to protective effect of 5,14-HEDGE against lipopolysaccharide-induced septic shock. International Journal of Pharmacology, 13(6), 654-666. https://doi.org/10.3923/ijp.2017.654.666

Inhibition of NLRP3 inflammasome contributes to protective effect of 5,14-HEDGE against lipopolysaccharide-induced septic shock. / Tunctan, Bahar; Kucukkavruk, Sefika Pinar; Temiz-Resitoglu, Meryem; Guden, Demet Sinem; Sari, Ayse Nihal; Sahan-Firat, Seyhan; Paudyal, Mahesh; Falck, J R; Malik, Kafait Ullah.

In: International Journal of Pharmacology, Vol. 13, No. 6, 2017, p. 654-666.

Research output: Contribution to journalArticle

Tunctan, B, Kucukkavruk, SP, Temiz-Resitoglu, M, Guden, DS, Sari, AN, Sahan-Firat, S, Paudyal, M, Falck, JR & Malik, KU 2017, 'Inhibition of NLRP3 inflammasome contributes to protective effect of 5,14-HEDGE against lipopolysaccharide-induced septic shock', International Journal of Pharmacology, vol. 13, no. 6, pp. 654-666. https://doi.org/10.3923/ijp.2017.654.666
Tunctan, Bahar ; Kucukkavruk, Sefika Pinar ; Temiz-Resitoglu, Meryem ; Guden, Demet Sinem ; Sari, Ayse Nihal ; Sahan-Firat, Seyhan ; Paudyal, Mahesh ; Falck, J R ; Malik, Kafait Ullah. / Inhibition of NLRP3 inflammasome contributes to protective effect of 5,14-HEDGE against lipopolysaccharide-induced septic shock. In: International Journal of Pharmacology. 2017 ; Vol. 13, No. 6. pp. 654-666.
@article{b3f2e67cfdab427392e6a1769635debd,
title = "Inhibition of NLRP3 inflammasome contributes to protective effect of 5,14-HEDGE against lipopolysaccharide-induced septic shock",
abstract = "Background and Objective: Nucleotide binding domain and leucine-rich repeat protein 3 (NLRP3) is reported to be involved in the pathogenesis of numerous inflammatory diseases including Alzheimer disease, Parkinson disease, Prion disease and type 2 diabetes mellitus. Previous studies have demonstrated that a stable synthetic analog of 20-hydroxyeicosatetraenoic acid (20-HETE), N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE), prevents vascular hyporeactivity, hypotension, tachycardia, inflammation and mortality in a rodent model of septic shock. This study was aimed to assess effect of 5,14-HEDGE on the changes in NLRP3/apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)/pro-caspase-1 inflammasome in lipopolysaccharide (LPS)-induced septic shock in rats. Methodology: Rats were injected with saline (4 mL kg-1) or LPS (10 mg kg-1) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. 5,14-HEDGE (30 mg kg-1) was administered to rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and kidney, heart, thoracic aorta and superior mesenteric artery were isolated for measurement of caspase-1/11 p20, NLRP3, ASC and β-actin proteins as well as interleukin-1β (IL-1β) levels. Data were analysed by one-way ANOVA followed by Student-Newman-Keuls test for multiple comparisons, Kruskal-Wallis test followed by Dunns test for multiple comparisons and Student's test or Mann-Whitney U tests when appropriate. Results: Blood pressure decreased by 33 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. In the LPS-treated rats, tissue protein expression of caspase-1/11 p20, NLRP3 and ASC in addition to IL-1β levels were increased. The 5,14-HEDGE prevented the LPS-induced changes. Conclusion: These findings suggest that inhibition of renal, cardiac and vascular formation/activity of NLRP3/ASC/pro-caspase-1 inflammasome involves in the protective effect of 5,14-HEDGE on LPS-induced septic shock in rats.",
keywords = "14-HEDGE, 20-HETE, 5, Blood pressure, Heart rate, IL-1β, Inflammation, Lipopolysaccharide, NLRP3 inflammasome",
author = "Bahar Tunctan and Kucukkavruk, {Sefika Pinar} and Meryem Temiz-Resitoglu and Guden, {Demet Sinem} and Sari, {Ayse Nihal} and Seyhan Sahan-Firat and Mahesh Paudyal and Falck, {J R} and Malik, {Kafait Ullah}",
year = "2017",
doi = "10.3923/ijp.2017.654.666",
language = "English (US)",
volume = "13",
pages = "654--666",
journal = "International Journal of Pharmacology",
issn = "1811-7775",
publisher = "Asian Network for Scientific Information",
number = "6",

}

TY - JOUR

T1 - Inhibition of NLRP3 inflammasome contributes to protective effect of 5,14-HEDGE against lipopolysaccharide-induced septic shock

AU - Tunctan, Bahar

AU - Kucukkavruk, Sefika Pinar

AU - Temiz-Resitoglu, Meryem

AU - Guden, Demet Sinem

AU - Sari, Ayse Nihal

AU - Sahan-Firat, Seyhan

AU - Paudyal, Mahesh

AU - Falck, J R

AU - Malik, Kafait Ullah

PY - 2017

Y1 - 2017

N2 - Background and Objective: Nucleotide binding domain and leucine-rich repeat protein 3 (NLRP3) is reported to be involved in the pathogenesis of numerous inflammatory diseases including Alzheimer disease, Parkinson disease, Prion disease and type 2 diabetes mellitus. Previous studies have demonstrated that a stable synthetic analog of 20-hydroxyeicosatetraenoic acid (20-HETE), N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE), prevents vascular hyporeactivity, hypotension, tachycardia, inflammation and mortality in a rodent model of septic shock. This study was aimed to assess effect of 5,14-HEDGE on the changes in NLRP3/apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)/pro-caspase-1 inflammasome in lipopolysaccharide (LPS)-induced septic shock in rats. Methodology: Rats were injected with saline (4 mL kg-1) or LPS (10 mg kg-1) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. 5,14-HEDGE (30 mg kg-1) was administered to rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and kidney, heart, thoracic aorta and superior mesenteric artery were isolated for measurement of caspase-1/11 p20, NLRP3, ASC and β-actin proteins as well as interleukin-1β (IL-1β) levels. Data were analysed by one-way ANOVA followed by Student-Newman-Keuls test for multiple comparisons, Kruskal-Wallis test followed by Dunns test for multiple comparisons and Student's test or Mann-Whitney U tests when appropriate. Results: Blood pressure decreased by 33 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. In the LPS-treated rats, tissue protein expression of caspase-1/11 p20, NLRP3 and ASC in addition to IL-1β levels were increased. The 5,14-HEDGE prevented the LPS-induced changes. Conclusion: These findings suggest that inhibition of renal, cardiac and vascular formation/activity of NLRP3/ASC/pro-caspase-1 inflammasome involves in the protective effect of 5,14-HEDGE on LPS-induced septic shock in rats.

AB - Background and Objective: Nucleotide binding domain and leucine-rich repeat protein 3 (NLRP3) is reported to be involved in the pathogenesis of numerous inflammatory diseases including Alzheimer disease, Parkinson disease, Prion disease and type 2 diabetes mellitus. Previous studies have demonstrated that a stable synthetic analog of 20-hydroxyeicosatetraenoic acid (20-HETE), N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE), prevents vascular hyporeactivity, hypotension, tachycardia, inflammation and mortality in a rodent model of septic shock. This study was aimed to assess effect of 5,14-HEDGE on the changes in NLRP3/apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)/pro-caspase-1 inflammasome in lipopolysaccharide (LPS)-induced septic shock in rats. Methodology: Rats were injected with saline (4 mL kg-1) or LPS (10 mg kg-1) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. 5,14-HEDGE (30 mg kg-1) was administered to rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and kidney, heart, thoracic aorta and superior mesenteric artery were isolated for measurement of caspase-1/11 p20, NLRP3, ASC and β-actin proteins as well as interleukin-1β (IL-1β) levels. Data were analysed by one-way ANOVA followed by Student-Newman-Keuls test for multiple comparisons, Kruskal-Wallis test followed by Dunns test for multiple comparisons and Student's test or Mann-Whitney U tests when appropriate. Results: Blood pressure decreased by 33 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. In the LPS-treated rats, tissue protein expression of caspase-1/11 p20, NLRP3 and ASC in addition to IL-1β levels were increased. The 5,14-HEDGE prevented the LPS-induced changes. Conclusion: These findings suggest that inhibition of renal, cardiac and vascular formation/activity of NLRP3/ASC/pro-caspase-1 inflammasome involves in the protective effect of 5,14-HEDGE on LPS-induced septic shock in rats.

KW - 14-HEDGE

KW - 20-HETE

KW - 5

KW - Blood pressure

KW - Heart rate

KW - IL-1β

KW - Inflammation

KW - Lipopolysaccharide

KW - NLRP3 inflammasome

UR - http://www.scopus.com/inward/record.url?scp=85024404359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85024404359&partnerID=8YFLogxK

U2 - 10.3923/ijp.2017.654.666

DO - 10.3923/ijp.2017.654.666

M3 - Article

VL - 13

SP - 654

EP - 666

JO - International Journal of Pharmacology

JF - International Journal of Pharmacology

SN - 1811-7775

IS - 6

ER -