Effect Of P120ctn On NF-κB Signaling Pathway In Airway Inflammatory Responses Induced By Formaldehyde

Formaldehyde (formaldehyde, FA) is a ubiquitous chemical pollutant; it has a strong pungent odor. Stimulation is the most common consequence of FA pollution; FA also can cause allergization, immune toxicity, neurotoxicity, genetic toxicity, reproductive toxicity, carcinogenicity and so on. Long-term exposure to FA can cause chronic respiratory disease, or damage DNA, induce mutations and increase the risk of suffering from a variety of malignant tumors.Airway is the first line to defense against harmful stimuli. Various harmful stimuli may cause lung infections. Airway epithelium starts their repair mechanisms after the injury.p120-catenin (p120), a member of the catenin family, which is not only involved in regulating intercellular connections and movements by cadherin complex and microtubule associated protein, but also translocated into the nucleus and bound with various transcription factors to regulate the transcription of target genes .NF-κB is normally sequestered in the cytoplasm of resting cells by inhibitor of NF-κB (IκB) and remains transcriptionally inactive. Stimulation by triggers such as FA induces the phosphorylation and degradation of IκB. The degradation of IκB exposes the nuclear localization signal sequence of NF-κB, leading to the nuclear translocation of NF-κB and transcriptional activation of its target genes. Recent research has shown that loss of p120 partcipates in the activation of NF-κB and the chronic skin inflammation, but it is uncertain whether p120 involves in airway inflammation through NF-κB signaling pathway. Therefore, our present studies focused on the effects of p120 on NF-κB signaling during the airway injury induced by FA, in order to clarify the repair of airway epithelium after injury and the molecular mechanisms of inflammation reactions.ObjectiveTo detect the changes of p120 expression and its on NF-κB signaling pathway during the inflammatory response induced by FA, to further analysis of mechanisms of airway inflammation. MethodsIn this study, we treated cells with FA to establish a airway inflammation model in vitro; the cells were incubated with FA at different times (1h, 2h, 3h, 4h); We observed the morphological changes of the cultured cells; Using Western blot and isolation of cytoplasmic and nuclear proteins, we examined the expressions of p120, NF-κB and IκBα; Then we detected the expressions of IL-8 by enzyme-linked immunosorbent assay (ELISA).Results1. Morphology of 16 HBE cells:In the common group, the 16HBE cells showed a classic cobblestone-like epithelial morphology that was three-dimensional and closely adherent. Treatment with FA made cells display morphological changes, including more widely flattened appearance, widened cell-cell interspaces. Higher concentration of FA made cells shrink to go round and dead numerously.2. Expressions of related factors:1) p120 was rich in 16 HBE cells, but reduced by FA.2) FA induced the activation of NF-κB signaling in 16 HBE cells, the expression of NF-κB p65 was increased.3) The translocation of p65 from cytoplasm to nucleus was confirmed by Western blot after FA treatment.4) IL-8, a proinflammatory factor, which is the target gene of NF-κB was also increased significantly after FA treatment.5) IκBαwas rapidly degradated by FA.Conclusions(1)FA induces the down-regulation of p120 in 16HBE cells.(2)FA induces NF-κB activation and IL-8 production.(3)The activation of NF-κB induced by FA may be accompanied with IκBαdegradation and p65 nuclear translocation in 16 HBE cells.(4)In the FA induced airway inflammation, p120 may negatively regulate NF-κB pathway activation, thus inhibit airway inflammation.