TLR2/NFκB signalling regulates endogenous IL-6 release from marrow-derived mesenchymal stromal cells to suppress the apoptosis of PC12cells injured by oxygen and glucose deprivation.

Abstract

Two previous studies published by our group identified that mesenchymal stromal cells (MSCs) conferred neuroprotection in a rat model of hypoxic-ischaemic brain damage (HIBD), and that MSCs secreted abundant interleukin-6 (IL‑6) when co‑cultured with oxygen and glucose deprivation (OGD)‑injured PC12cells. The present study has further investigated the role of IL‑6, and explored potential signalling pathways invitro. Invitro models were established by co‑culturing OGD‑injured PC12cells with MSCs. Subsequently, the expression levels of the signalling molecules, Toll‑like receptor2 (TLR2)/nuclear factorκB (NFκB), and IL‑6 were altered separately in this invitro model by treatment with an agonist, antagonist, siRNA or overexpression adenovirus. The expression levels of Bcell lymphoma‑associated X (Bax), TLR2, NFκB and IL‑6 were detected by western blot analysis, real‑time polymerase chain reaction or ELISA. The resting membrane potential (RMP) of the PC12cells was analysed by whole‑cell patch‑clamp recordings. Compared with controls or the PC12 co‑culture group, the MSC co‑cultured group induced less expression of Bax, but more IL‑6 secretion. Up- or down-regulation of the TLR2/NFκB signalling pathway resulted in a corresponding increase or decrease in the IL‑6 expression level in the MSCs. Co‑culture with siIL‑6‑MSCs increased the expression levels of Bax and increased the RMP in the OGD PC12cells. In conclusion, the release of IL‑6 from MSCs was regulated via the TLR2/NFκB signalling pathway. Endogenous IL‑6 reduced apoptosis and protected OGD‑injured PC12cells when they were co‑cultured with MSCs. The present study has reported a novel immunomodulatory effect of the microenvironment of neural damage during MSC cytotherapy.