ABSTRACT
Curcumin (CUR) possesses the capability to inhibit various inflammatory factors, exert anti-inflammatory effects, and alleviate asthma attacks; however, its hydrophobicity and instability significantly impede its clinical application. In this study, we synthesized CUR-loaded nanoparticles (CUR-NPs) and evaluated their impact on the proliferation, migration, and inflammatory infiltration of mouse airway smooth muscle cells (ASMCs), while investigating their underlying mechanisms. To achieve this objective, ASMCs were isolated from BALB/c mice and subjected to TGF-ß1-induced cell proliferation and migration. Our findings demonstrate that CUR-NPs effectively regulate the release of CUR within cells with superior intracellular uptake compared to free CUR. The CCK-8 assay results indicate that the blank carrier does not exhibit any cytotoxic effects on cells, thus rendering the impact of the carrier itself negligible. The TGF-ß1 group exhibited a significant increase in cell proliferation, whereas treatment with CUR-NPs significantly suppressed TGF-ß1-induced cell proliferation. The findings from both the cell scratch assay and transwell assay demonstrated that TGF-ß1 substantially enhanced cell migration, while CUR-NPs treatment effectively attenuated TGF-ß1-induced cell migration. The Western blot analysis demonstrated a substantial increase in the expression levels of TGF-ß1, p-STAT3, and CTGF in ASMCs following treatment with TGF-ß1 when compared to the control group. Nevertheless, this effect was effectively counteracted upon administration of CUR-NPs. Furthermore, an asthma mouse model was successfully established and CUR-NPs were administered through tail vein injection. The serum levels of TGF-ß1 and the expression levels of TGF-ß1, p-STAT3, and CTGF proteins in the lung tissue of mice in the model group exhibited significant increases compared to those in the control group. However, CUR-NPs treatment effectively attenuated this change. Our research findings suggest that CUR-NPs possess inhibitory effects on ASMC proliferation, migration, and inflammatory infiltration by suppressing activation of the TGF-ß1/p-STAT3/CTGF signaling pathway, thereby facilitating inhibition of airway remodeling.
ABSTRACT
BACKGROUND: The tumour microenvironment reshapes the specific gene expression of regulatory T cells (Tregs). A better definition of Treg subpopulations in the non-small-cell lung cancer (NSCLC) milieu is expected to clarify the identity and functional mode of Tregs and lead to the identification of better therapeutic targets. METHODS: A total of 53 peripheral blood (PB) samples from 36 NSCLC patients and 17 control subjects and 42 matched bronchoalveolar lavage fluid (BALF) samples from 31 NSCLC patients and 11 control subjects were obtained to examine the frequencies of Treg subgroups through flow cytometry. Fifteen PB samples from healthy individuals were collected to explore the differential functions of Treg subsets. The PB samples of 5 patients after chemotherapy were obtained to evaluate the effect of chemotherapy on Treg subsets. Serum CYFRA 21-1 levels in NSCLC patients were determined using an electrochemiluminescence immunoassay. RESULTS: The proportions of CD4+CD25+FoxP3+ Tregs in both PB and BALF were increased in NSCLC patients compared to controls. In BALF, the TIGIT+, Helios+, and TIGIT+Helios+ Treg subset levels were significantly elevated; the levels of the last two subsets were associated with NSCLC development, while the level of TIGIT-Helios- Tregs was decreased. The proportions of overall Tregs and TIGIT+, Helios+, and Helios+TIGIT+ Tregs were positively correlated with the serum CYFRA 21-1 levels in all patients. Functional differences were observed between Helios+TIGIT+ and Helios-TIGIT- Tregs. After chemotherapy, regardless of the reduction in serum CYFRA 21-1 levels, the proportions of Tregs and Treg subsets did not change. CONCLUSIONS: Elevated TIGIT+Helios+ and Helios+ Treg levels may play a role in NSCLC tumour progression, and targeting TIGIT and Helios on Tregs may be an effective treatment for NSCLC.
