TLR4 knock out alleviate both lung and liver inflammation caused by short-time exposure to PM2.5

Abstract

Background: Ambient particulate matter (PM), a principal component of air pollutant, is harmful to human health in many ways. Toll-like receptors (TLRs) are non-catalytic transmembrane protein that can identify conservative molecules from microorganisms. However, the regulatory mechanism of TLR4 and its effects on lung and liver inflammation induced by PM are unknown presently. Method: Wild type mice and TLR4-/- mice (C57BL/10JNju, mixed gender, 8-10 weeks old,), both were randomly divided into two groups. The mice were intratracheally instilled with saline or PM2.5 (4 mg/kg) every other day and continued for 10 days. Result: PM2.5 increased the BCA and Lactate Dehydrogenase (LDH) level and TLR4 KO mice showed lower BCA compared to wild type mice(P=0.08). PM2.5 treatment increased the expression of inflammatory cytokines (HMGB1, TNFα, MCP-1/CCL2, CCR2) significantly compared to the saline treatment (P<0.05) and there is a trend that this could be attenuated in TLR4 knock out mice. HE staining showed that PM2.5 induced severe inflammatory damage, and TLR4 KO could alleviate the process of inflammation. As to the liver, LDH and Alkaline Phosphatase (AKP) significantly increased in PM2.5 treatment only in wild type mice. Similar to the lung tissue, PM2.5 stimulation resulted in robust induction of proinflammatory genes expression levels, and TLR4 KO could alleviate the progression of liver inflammation. Conclusion: Our findings suggest that, TLR4 plays an important role in regulating lung and liver inflammatory response caused by PM2.5.