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Toll-like receptor 4 involvement in hepatic ischemia/reperfusion injury in mice.
Hepatobiliary Pancreat Dis Int. 2004 May; 3(2):250-3.HP

Abstract

BACKGROUND

Toll-like receptor 4 (TLR4) is involved in innate immunity by recognizing endotoxin resulting in a burst of inflammatory cascade. We investigated the relation between activation of TLR4 and liver injury in partial hepatic ischemia/reperfusion (I/R) injury in mice.

METHODS

TLR4-deficient mice (C3H/Hej) and wild type mice (WT, C3H/Heouj) were used in the model of I/R injury. Partial hepatic ischemia was produced by occlusion of inflow to the median and left lobes for 45 minutes. Blood was drawn at 1 and 3 hours after reperfusion. The blood was analyzed for aspartate aminotransferase (AST) and tumor necrosis factor alpha (TNF-alpha). TNF-alpha mRNA expression and myeloperoxidase (MPO) level in the ischemic lobes were examined by northern blot and myeloperoxidase assay respectively.

RESULTS

AST levels were significantly decreased in TLR4deficient mice compared with WT mice at both time points (WT: 1215.5+/-174.03, 2958.17+/-186.81 IU/L at 1 and 3 hours respectively vs TLR4def: 661.83+/-106.09, 1145.17+/-132.43 IU/L at 1 and 3 hours, mean+/-SD, 6 mice/group, t=-6.65 and -5.57, P<0.001). Consistent with the role of TNF-alpha in hepatic I/R, serum TNF-alpha was decreased in TLR4 deficient mice at 3 hours after reperfusion compared with WT (152.39+/-43.3 vs 249.12+/-51.89, n=6, t=-3.13, P<0.05). MPO level in the ischemic lobes in TLR4 deficient mice at 3 hours after reperfusion was significantly lower than that in WT mice (0.059 +/-0.004 vs 0.173+/-0.025, n=6, F=33.49, P<0.001). This difference appears to be mediated at the gene level since TLR4 deficient mice had decreased TNF-alpha mRNA expression at 1 hour after reperfusion compared with WT mice (80.3+/-28.8 vs 189.4+/-24.6, t=-3.25, P<0.05).

CONCLUSIONS

Compared with WT mice, TLR4-deficient mice appear to have a mild I/R injury. Regulation of TNF-alpha at mRNA level seems to have a critical effect. These suggest TLR4 be involved in the mechanism of hepatic I/R injury in mice.

Authors+Show Affiliations

Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. hs1898@public.wh.hb.cnNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15138120

Citation

Wu, He-Shui, et al. "Toll-like Receptor 4 Involvement in Hepatic Ischemia/reperfusion Injury in Mice." Hepatobiliary & Pancreatic Diseases International : HBPD INT, vol. 3, no. 2, 2004, pp. 250-3.
Wu HS, Zhang JX, Wang L, et al. Toll-like receptor 4 involvement in hepatic ischemia/reperfusion injury in mice. Hepatobiliary Pancreat Dis Int. 2004;3(2):250-3.
Wu, H. S., Zhang, J. X., Wang, L., Tian, Y., Wang, H., & Rotstein, O. (2004). Toll-like receptor 4 involvement in hepatic ischemia/reperfusion injury in mice. Hepatobiliary & Pancreatic Diseases International : HBPD INT, 3(2), 250-3.
Wu HS, et al. Toll-like Receptor 4 Involvement in Hepatic Ischemia/reperfusion Injury in Mice. Hepatobiliary Pancreat Dis Int. 2004;3(2):250-3. PubMed PMID: 15138120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Toll-like receptor 4 involvement in hepatic ischemia/reperfusion injury in mice. AU - Wu,He-Shui, AU - Zhang,Jin-Xiang, AU - Wang,Lin, AU - Tian,Yuan, AU - Wang,Hui, AU - Rotstein,Ori, PY - 2004/5/13/pubmed PY - 2004/7/16/medline PY - 2004/5/13/entrez SP - 250 EP - 3 JF - Hepatobiliary & pancreatic diseases international : HBPD INT JO - Hepatobiliary Pancreat Dis Int VL - 3 IS - 2 N2 - BACKGROUND: Toll-like receptor 4 (TLR4) is involved in innate immunity by recognizing endotoxin resulting in a burst of inflammatory cascade. We investigated the relation between activation of TLR4 and liver injury in partial hepatic ischemia/reperfusion (I/R) injury in mice. METHODS: TLR4-deficient mice (C3H/Hej) and wild type mice (WT, C3H/Heouj) were used in the model of I/R injury. Partial hepatic ischemia was produced by occlusion of inflow to the median and left lobes for 45 minutes. Blood was drawn at 1 and 3 hours after reperfusion. The blood was analyzed for aspartate aminotransferase (AST) and tumor necrosis factor alpha (TNF-alpha). TNF-alpha mRNA expression and myeloperoxidase (MPO) level in the ischemic lobes were examined by northern blot and myeloperoxidase assay respectively. RESULTS: AST levels were significantly decreased in TLR4deficient mice compared with WT mice at both time points (WT: 1215.5+/-174.03, 2958.17+/-186.81 IU/L at 1 and 3 hours respectively vs TLR4def: 661.83+/-106.09, 1145.17+/-132.43 IU/L at 1 and 3 hours, mean+/-SD, 6 mice/group, t=-6.65 and -5.57, P<0.001). Consistent with the role of TNF-alpha in hepatic I/R, serum TNF-alpha was decreased in TLR4 deficient mice at 3 hours after reperfusion compared with WT (152.39+/-43.3 vs 249.12+/-51.89, n=6, t=-3.13, P<0.05). MPO level in the ischemic lobes in TLR4 deficient mice at 3 hours after reperfusion was significantly lower than that in WT mice (0.059 +/-0.004 vs 0.173+/-0.025, n=6, F=33.49, P<0.001). This difference appears to be mediated at the gene level since TLR4 deficient mice had decreased TNF-alpha mRNA expression at 1 hour after reperfusion compared with WT mice (80.3+/-28.8 vs 189.4+/-24.6, t=-3.25, P<0.05). CONCLUSIONS: Compared with WT mice, TLR4-deficient mice appear to have a mild I/R injury. Regulation of TNF-alpha at mRNA level seems to have a critical effect. These suggest TLR4 be involved in the mechanism of hepatic I/R injury in mice. SN - 1499-3872 UR - https://www.unboundmedicine.com/medline/citation/15138120/Toll_like_receptor_4_involvement_in_hepatic_ischemia/reperfusion_injury_in_mice_ L2 - https://medlineplus.gov/liverdiseases.html DB - PRIME DP - Unbound Medicine ER -