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
N1 - Publisher Copyright:
© 2017 Bahar Tunctan et al.
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
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U2 - 10.3923/ijp.2017.654.666
DO - 10.3923/ijp.2017.654.666
M3 - Article
AN - SCOPUS:85024404359
SN - 1811-7775
VL - 13
SP - 654
EP - 666
JO - International Journal of Pharmacology
JF - International Journal of Pharmacology
IS - 6
ER -