Dynamic expressions of interleukin-1 receptor associated kinase-4 and interleukin-1 receptor associated kinase-M in rats with endotoxin tolerance and their significance / 中华传染病杂志

ABSTRACT

Objective To explore the dynamic expressions of interleukin-1 (IL-1)receptor associated kinase (IRAK)-M and IRAK-4 in rats with or without endotoxin tolerance (ETT)in acute liver failure (ALF).Methods Sixty-six male SD rats were divided into three groupsALF group,ETT group and control group.The rats in ETT group received daily lipopolysaccharide (LPS)intraperitoneal injection for 5 days,while the rats in ALF group received daily injection with same volume of 0.75% NaCl solution.Both ETT group and ALF group received intraperitoneal injection with D-galactosamine (D-GalN)and LPS at 24 hours after the 5th injection of LPS or NaCl solution.At 2,6,12,24 and 48 h after D-GalN and LPS injection,the serum levels of tumor necrosis factor-α (TNF-α)and interleukin-6 (IL-6)were detected by enzyme-linked immunosorbent assay (ELISA).The liver pathologic changes were observed with HE staining by microscope.The mRNA expressions of IRAK-4,IRAK-M and NF-κB (p65)were detected by reverse transcriptase polymerase chain reaction (RT-PCR).The pairwise comparison between groups was done by lease significant difference (LSD)and Dunnet's t test.Results The liver pathologic changes in ETT group were much milder than those of ALF group.In ALF group,IRAK-4 mRNA/β-actin absorbance ratios at 2,6,12,24and 48 h after D-GalN and LPS challenge were 0.711 ±0.074,0.904±0.118,1.012 ±0.098,1.534±0.279 and 1.451±0.290,respectively,while the IRAK-M mRNA/β-actin absorbance ratios were 0.496±0.018,0.516±0.089,0.503±0.023,0.503±0.057 and 0.469±0.142,respectively.In ETT group,the IRAK-4 mRNA/β-actin absorbance ratios at 2,6,12,24 and 48 h after D-GalN and LPS challenge were 0.619±0.083,0.587±0.033,0.623±0.034,0.720±0.044 and 0.654±0.041,respectively,while the IRA'K-M mRNA/β-actin absorbance ratios were 0.929 ± 0.064,1.111±0.138,1.113±0.027,1.891±0.315 and 1.710±0.303,respectively.The IRAK-M mRNA expression level was significantly increased and IRAK-4 mRNA expression level was relatively decreased in ETT group compared to ALF group.The differences were all statistically significant at 2,6,12,24 and 48 h after D-GalN and LPS challenge (F= 17.305,54.921,121.031,67.607,55.279,respectively; F=19.506,43.777,110.823,302.681,202.822,respectively; F=172.003,59.519,987.055,68.463,96.601,respectively; all P＜0.05).Conclusion LPS pretreatment may induce ETT in rat model by downregulating the expression of IRAK-4 and upregulating the expression of IRAK-M.