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Neutrophil elastase contributes to the development of ischemia/reperfusion-induced liver injury by decreasing the production of insulin-like growth factor-I in rats.
Transl Res. 2010 Jun; 155(6):294-304.TR

Abstract

Neutrophil elastase (NE) decreases the endothelial production of prostacyclin (PGI(2)) through the inhibition of endothelial nitric oxide synthase (NOS) activation and thereby contributes to the development of ischemia/reperfusion (I/R)-induced liver injury. We previously demonstrated that calcitonin gene-related peptide (CGRP) released from sensory neurons increases the insulin-like growth factor- I (IGF-I) production and thereby reduces I/R-induced liver injury. Because PGI(2) is capable of stimulating sensory neurons, we hypothesized that NE contributes to the development of I/R-induced liver injury by decreasing IGF-I production. In the present study, we examined this hypothesis in rats subjected to hepatic I/R. Ischemia/reperfusion-induced decreases of hepatic tissue levels of CGRP and IGF-I were prevented significantly by NE inhibitors, sivelestat, and L-658, 758, and these effects of NE inhibitors were reversed completely by the nonselective cyclooxygenase inhibitor indomethacin (IM) and the nonselective NOS inhibitor L-NAME but not by the selective inducible NOS inhibitor 1400W. I/R-induced increases of hepatic tissue levels of caspase-3, myeloperoxidase and the number of apoptotic cells were inhibited by NE inhibitors, and these effects of NE inhibitors were reversed by IM and L-NAME but not by 1400W. Administration of iloprost, a stable PGI(2) analog, produced effects similar to those induced by NE inhibitors. Taken together, these observations strongly suggest that NE may play a critical role in the development of I/R-induced liver injury by decreasing the IGF-I production through the inhibition of sensory neuron stimulation, which may lead to an increase of neutrophil accumulation and hepatic apoptosis through activation of caspase-3 in rats.

Authors+Show Affiliations

Department of Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20478544

Citation

Kawai, Miho, et al. "Neutrophil Elastase Contributes to the Development of Ischemia/reperfusion-induced Liver Injury By Decreasing the Production of Insulin-like Growth factor-I in Rats." Translational Research : the Journal of Laboratory and Clinical Medicine, vol. 155, no. 6, 2010, pp. 294-304.
Kawai M, Harada N, Takeyama H, et al. Neutrophil elastase contributes to the development of ischemia/reperfusion-induced liver injury by decreasing the production of insulin-like growth factor-I in rats. Transl Res. 2010;155(6):294-304.
Kawai, M., Harada, N., Takeyama, H., & Okajima, K. (2010). Neutrophil elastase contributes to the development of ischemia/reperfusion-induced liver injury by decreasing the production of insulin-like growth factor-I in rats. Translational Research : the Journal of Laboratory and Clinical Medicine, 155(6), 294-304. https://doi.org/10.1016/j.trsl.2010.02.003
Kawai M, et al. Neutrophil Elastase Contributes to the Development of Ischemia/reperfusion-induced Liver Injury By Decreasing the Production of Insulin-like Growth factor-I in Rats. Transl Res. 2010;155(6):294-304. PubMed PMID: 20478544.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neutrophil elastase contributes to the development of ischemia/reperfusion-induced liver injury by decreasing the production of insulin-like growth factor-I in rats. AU - Kawai,Miho, AU - Harada,Naoaki, AU - Takeyama,Hiromitsu, AU - Okajima,Kenji, Y1 - 2010/03/19/ PY - 2009/09/15/received PY - 2010/01/26/revised PY - 2010/02/22/accepted PY - 2010/5/19/entrez PY - 2010/5/19/pubmed PY - 2010/6/4/medline SP - 294 EP - 304 JF - Translational research : the journal of laboratory and clinical medicine JO - Transl Res VL - 155 IS - 6 N2 - Neutrophil elastase (NE) decreases the endothelial production of prostacyclin (PGI(2)) through the inhibition of endothelial nitric oxide synthase (NOS) activation and thereby contributes to the development of ischemia/reperfusion (I/R)-induced liver injury. We previously demonstrated that calcitonin gene-related peptide (CGRP) released from sensory neurons increases the insulin-like growth factor- I (IGF-I) production and thereby reduces I/R-induced liver injury. Because PGI(2) is capable of stimulating sensory neurons, we hypothesized that NE contributes to the development of I/R-induced liver injury by decreasing IGF-I production. In the present study, we examined this hypothesis in rats subjected to hepatic I/R. Ischemia/reperfusion-induced decreases of hepatic tissue levels of CGRP and IGF-I were prevented significantly by NE inhibitors, sivelestat, and L-658, 758, and these effects of NE inhibitors were reversed completely by the nonselective cyclooxygenase inhibitor indomethacin (IM) and the nonselective NOS inhibitor L-NAME but not by the selective inducible NOS inhibitor 1400W. I/R-induced increases of hepatic tissue levels of caspase-3, myeloperoxidase and the number of apoptotic cells were inhibited by NE inhibitors, and these effects of NE inhibitors were reversed by IM and L-NAME but not by 1400W. Administration of iloprost, a stable PGI(2) analog, produced effects similar to those induced by NE inhibitors. Taken together, these observations strongly suggest that NE may play a critical role in the development of I/R-induced liver injury by decreasing the IGF-I production through the inhibition of sensory neuron stimulation, which may lead to an increase of neutrophil accumulation and hepatic apoptosis through activation of caspase-3 in rats. SN - 1878-1810 UR - https://www.unboundmedicine.com/medline/citation/20478544/Neutrophil_elastase_contributes_to_the_development_of_ischemia/reperfusion_induced_liver_injury_by_decreasing_the_production_of_insulin_like_growth_factor_I_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1931-5244(10)00052-6 DB - PRIME DP - Unbound Medicine ER -