Human umbilical cord mesenchymal stem cells derived-exosomes alleviate LPS-induced cervical inflammation and epithelial-mesenchymal transition.

OBJECTIVE

Patients with chronic cervicitis are known to have an increased risk of infection with human papillomavirus (HPV), which is the primary cause of cervical cancer. Inhibition of cervical inflammation may reduce the risk of cervical cancer. This study investigated how human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) attenuated the lipopolysaccharide (LPS)-induced cervical inflammation.

METHODS

Human uterine squamous carcinoma (SiHa) cells were induced with LPS to construct an inflammatory model and treated with hucMSC-Ex. The expression levels of tumor necrosis factor α (TNF-α), and interleukins (IL)-1β, IL-6, IL-10 were analyzed by qRT-PCR. Western blot was used to detect the protein expression levels of cyclooxygenase-2 (COX-2) and proliferating cell nuclear antigen (PCNA) in cells, and CCK8 was used to examine cell proliferation, so as to explore the relieving effect of hucMSC-Ex on cell inflammation. The expression of epithelial-mesenchymal transition (EMT) markers in SiHa cells was also assessed by qRT-PCR and western blot to determine the effect of hucMSC-Ex on inflammation. Moreover, clinical cervical smears were collected to detect the expression of EMT markers in clinical exfoliated cell samples by immunofluorescence.

RESULTS

HucMSC-Ex treatment significantly reduced the expression of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6 in the LPS-induced inflammation model, while increasing the level of anti-inflammatory cytokines, including IL-10, to reduce inflammation. HucMSC-Ex increased the expression level of epithelial markers (such as E-cadherin) while it decreased the expression of interstitial markers (such as N-cadherin), suggesting it inhibits EMT.

CONCLUSIONS

Our results support that hucMSC-Ex alleviates LPS-induced cervical inflammation, possibly by inhibition of EMT.