Foxp3 expression in A549 cells is regulated by Toll-like receptor�4 through nuclear factor-κB

Abstract

Abstract. Foxp3 is a master regulator of the development and function of CD4 + CD25 + regulatory T cells (Tregs). Previous studies have reported that Foxp3 is also expressed in tumour cells and promotes tumour immune evasion. However, the regulation of the expression of Foxp3 in tumour cells remains unclear. Toll-like receptor 4 (TLR4), a member of the pattern recognition receptor family, is also expressed in tumour cells. Previous studies have found that the TLR4 signaling pathway is involved in tumour immune evasion in lung cancer cells, and that the transcription factor, nuclear factor-κB (NF-κB), plays a key role in the TLR4 signaling pathway. Moreover, recent studies found that NF-κB promotes the transcription of Foxp3. We hypothesised that TLR4 may also be involved in the regulation of Foxp3 in A549 cells through NF-κB. Therefore, we examined the effect of TLR4 and NF-κB on the expression of Foxp3 in the A549 lung cancer cell line. The results showed that Foxp3 and TLR4 are expressed in A549 cells; the expression of Foxp3 increased after lipopolysaccharide (LPS) stimulation and decreased after blocking the TLR4 signaling pathway. In addition, the expression of NF-κB (p65) increased after LPS stimulation and the expression of Foxp3 decreased after blocking NF-κB. These results suggest that TLR4 is involved in the regulation of Foxp3 in A549 cells through NF-κB.

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“…However, Chu et al demonstrated that FOXP3 depletion downregulated cyclin D1 and NF-κB subunit p65, but upregulated caspase-3 levels in K1 and WRO thyroid cancer cells [182]. Also, Jia et al indicated that blockade of toll-like receptor 4 (TLR4) signaling induced downregulation of FOXP3 after blocking NF-κB in A549 cells [183]. Here microenvironmental conditions where FOXP3 acts as a tumor suppressor or an oncogene should be clearly determined in specific cancers in association with TRL4, NFAT and NF-κB signaling in the future.…”