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We found that both mRNA and protein levels of TLR4 and TLR9 were strongly expressed in lung cancer tissue. In addition, we reported for the first time a positive correlation between the expression level of TLR4 and malignancy of lung cancer. These results suggested that TLR4 and TLR9 may be involved in the development of lung cancer which may have the potentials for the treatment of this malignant tumor.

Notch3 receptor is one of the mammalian Notch family receptors (Notch1-4) which plays an important role in the regulation of cellular proliferation, differentiation, and apoptosis. Overexpression of Notch3 is associated with tumorigenesis. In order to assess the expression of Notch3 in Chinese non-small-cell lung cancer (NSCLC) patients and determine its association with prognosis, we designed a prospective study with five years of follow-up to evaluate Notch3 expression in NSCLC tissues and adjacent non-cancerous normal lung tissues from 131 patients undergoing surgical treatment by immunohistochemistry and western blot analysis. Notch3 had high expression in 67 of 131 cases of NSCLC (51.1 %), which was significantly higher than in adjacent noncancerous lung tissues. Moreover, Notch3 overexpression was significantly correlated with TNM stage (P = 5.41e-07 in squamous cell carcinoma, P = 5.338e-07 in adenocarcinoma) and lymph node metastasis (P = 0.00764 in squamous cell carcinoma, P = 0.01491 in adenocarcinoma). Kaplan-Meier survival analysis showed that the overall survival times in patients expressing Notch3 in NSCLC were shorter. Multivariate analysis further demonstrated that Notch3 was an independent prognostic factor for patients with NSCLC. Therefore, Notch3 might be a useful biomarker to predict the prognosis of patients with NSCLC.

Exposure to fine particulate matter (PM2.5) has been associated with lung inflammation and airway hyperresponsiveness (AHR). Transient receptor potential (TRP) vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) both may play important roles in lung inflammation and AHR. We investigated whether PM2.5-induced lung inflammation and AHR could be prevented by blocking TRPV1 and TRPA1 channels. Mice were injected intraperitoneally with AMG9810 (30 mg/kg, a TRPV1 antagonist) or A967079 (30 mg/kg, a TRPA1 antagonist) or their combination or vehicle (PBS) one hour before intranasal instillation of PM2.5 (7.8 mg/kg) or vehicle (PBS) for two consecutive days, and then the mice were studied 24 h later. All pretreatments inhibited PM2.5-induced AHR and inflammatory infiltration in the lung tissue and decreased inflammatory cytokine levels in the bronchoalveolar lavage fluid, together with oxidant levels in the lung. AMG9810 inhibited MFF expression and increased MFN2 expression while A967079 inhibited DRP1 expression and increased OPA1 expression; combined pretreatment reduced MFF and DPR1 expression and increased MFN2 and OPA1 expression. All pretreatments inhibited the activation of the TLR4/NF-κB pathway, while A967079 alone, and combined with AMG9810 also reduced the activation of the NLRP3/caspase-1 pathway. Both TRPV1 and TRPA1 channels play an important role in PM2.5-induced lung inflammation and AHR. However, inhibition of the TRPA1 channel or combined inhibition of TRPA1 and TRPV1 channels resulted in greater inhibitory effect on PM2.5-induced lung injury through regulating the mitochondrial fission/fusion proteins and inhibiting the TLR4/NF-κB and NLRP3/caspase-1 pathways.

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