Abstract:
Background Trichloroethylene (TCE) can cause occupational drug-like dermatitis with severe liver damage, which is one of the leading causes of death, but its mechanism is still unclear.
Objective This study observes the polarization of Kupffer cells (KCs) in the liver of TCE sensitized mice, and to explore the role of M1 type polarization of KCs in immune liver injury induced by TCE.
Methods Thirty-six female BALB/c mice, 6-8 weeks old, were randomly divided into four groups:blank control group (n=5), vehicle control group (n=5), TCE-treated group (TCE group, n=11), and inhibitor-treated group (TCE+GdCl3 group, n=15), with adaptive feeding for one week. A TCE sensitization model was established according to an protocol developed by our team. Twenty-four hours after the last challenge, the skin of the TCE group and the TCE+GdCl3 group was scored and the mice in the TCE group and the TCE+GdCl3 group were divided into sensitization positive group and sensitization negative group. Seventy-two hours after the last challenge, the mice were sacrificed and the livers were taken. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) as selected liver injury indicators were determined using automatic biochemical analyzer; the pathological changes of liver were observed after HE staining; the expression level of surface marker F4/80 of KCs was detected by immunohistochemistry; the expression level of surface marker CD11c in M1 type macrophages was detected by immunofluorescence; and the expression level of tumor necrosis factor (TNF)-α in mouse liver was detected by immunohistochemistry.
Results The sensitization rate was 45.45% (5/11) in the TCE group and 33.33% in the TCE+GdCl3 group (5/15), with no significant difference (P>0.05). The serum ALT and AST levels were not significantly different between the blank control group and the vehicle control group (P>0.05). Compared with the vehicle control group and the TCE negative group, the serum ALT and AST levels were significantly increased in the TCE positive group (P < 0.05). The ALT level and AST level in the TCE positive group were (115.05±13.74) U/L and (224.68±30.98) U/L, respectively; the levels in the TCE+GdCl3 positive group were (97.59±9.16) U/L and (124.69±11.26) U/L, respectively, lower than those in the TCE positive group (P < 0.05). The results of HE staining showed that the liver cells of the control groups and the negative groups were normal in morphology and color; in the TCE positive group, the cells had abnormal cell morphology and vacuolar degeneration; some cells in the liver of the TCE+GdCl3 positive group showed edema. The immunohistochemical results of liver F4/80 showed that the expression levels in the blank control group and the vehicle control group were low, the TCE positive group had more deposition of F4/80 than the vehicle control group, while the TCE+GdCl3 positive group had less than the TCE positive group (P < 0.05). The results of liver CD11c immunofluorescence showed that the expression levels were low in the blank control group and the vehicle control group, the expression level of CD11c was higher in the TCE positive group than in the vehicle control group, while the expression level of this index was lower in the TCE+GdCl3 positive group than in the TCE positive group. The results of immunohistochemistry showed that the expression levels of TNF-α were very low in the blank control group and the vehicle control group, and higher in the TCE positive group than in the vehicle control group, and lower in the TCE+GdCl3 positive group than in the TCE positive group (P < 0.05).
Conclusion KCs play an important role in immune liver injury induced by TCE in mice, and M1 type polarization may aggravate the injury.
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