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Published on: October 22, 2012
Effects of myeloperoxidase on inflammatory responses with hypoxia in Citrobacter rodentium-infectious mice
Xiang Gao1,2,3, Yu Zhang1, Qinfang Zhu2,3
1Department of Basic Medical Sciences, Medical College, Qinghai University, Xining, Qinghai, China.
Purpose:
Myeloperoxidase (MPO) has been identified as a mediator in various inflammatory diseases. Bacterial infection of the intestine and hypoxia can both lead to inflammatory responses, but the role of MPO in these phenomena remains unclear.
Methods:
By building the MPO-/- mice, we evaluated relevant inflammatory factors and tissue damage in mice with intestinal Citrobacter rodentium infection and hypoxia. The body weight and excreted microorganisms were monitored. Intestinal tissues were collected 7 days after bacterial infection under hypoxia to undergo haematoxylin-eosin staining and assess the degree of pathological damage. ELISA assays were performed to quantify the serum levels of TNF-α, IFN-γ, IL-6, and IL-1β inflammatory cytokines. PCR, WB, and IF assays were conducted to determine the expression of chemokines MCP1, MIP2, and KC in the colon and spleen.
Results:
The C. rodentium infection and hypoxia caused weight loss, intestinal colitis, and splenic inflammatory cells active proliferation in wild-type mice. MPO deficiency alleviated this phenomenon. MPO-/- mice also displayed a significant decline in bacteria clearing ability. The level of TNF-α in the serum and spleen was both lower in MPO-/- hypoxia C. rodentium-infected mice than that in wild-type mice. The chemokines expression levels of MIP2, KC, and MCP1 in the spleen and colon of each bacterial infected group were significantly increased (p < .05), while in hypoxia, the factors in the spleen and colon were decreased (p < .05). MPO deficiency was found to lower the levels of these chemokines compared with wild-type mice.
Conclusion:
MPO plays an important role of the inflammatory responses in infectious enteritis and hypoxia in mice, and the loss of MPO may greatly reduce the body's inflammatory responses to fight diseases.
Insights
Myeloperoxidase (MPO) deficiency alleviates inflammatory responses during bacterial enteritis and hypoxia in mice. Loss of MPO reduces inflammation but impairs bacterial clearance, highlighting its complex role in infection.
Area of Science:
- Immunology
- Microbiology
- Pathology
Background:
- Myeloperoxidase (MPO) is implicated in inflammatory diseases.
- The role of MPO in infectious enteritis and hypoxia is not well understood.
Purpose of the Study:
- To investigate the role of MPO in mice with intestinal Citrobacter rodentium infection and hypoxia.
- To evaluate inflammatory factors and tissue damage in MPO-deficient mice.
Main Methods:
- Mice lacking MPO (MPO-/-) were infected with C. rodentium under hypoxic conditions.
- Assessed body weight, microbial counts, intestinal pathology (H&E staining), serum cytokines (ELISA), and chemokine expression (PCR, WB, IF).
Main Results:
- MPO-/- mice showed alleviated weight loss, colitis, and splenic inflammation compared to wild-type mice.
- Bacterial clearance was reduced in MPO-/- mice.
- MPO deficiency lowered TNF-α levels and suppressed chemokine expression (MCP1, MIP2, KC) in the colon and spleen.
Conclusions:
- MPO is crucial for inflammatory responses in infectious enteritis and hypoxia.
- MPO deficiency reduces inflammation but may compromise the ability to fight infection.
