Inflammatory profiling of Schwann cells manifested as an upregulation of cytokines is present after traumatic or disease injury of the peripheral nerves. Inflammatory activation of Schwann cells via Toll-like receptors (TLRs) can be triggered by exogenous pathological molecules or endogenous ligands produced during Wallerian degeneration. We investigated the early period of inflammatory reactions by following the levels of TLR4, NFκB, IL-1β, pSTAT3, and IL-6 proteins after LPS treatment of RT4 schwannoma cells under in vitro conditions. Significantly increased levels of NFκB, IL-1β, pSTAT3, and IL-6 proteins were found 1 h after LPS action indicating their involvement in the initiation of the inflammatory reaction of schwannoma cells. This initiation was induced without increased TLR4 protein expression, but was accompanied by the appearance of TLR4 in early endosomes. The protein levels decreased within the next 6 h of treatment with a subsequent increase of NFκB, IL-1β, and pSTAT3 after 24 h of LPS treatment. In contrast, continuous decrease of IL-6 over time following LPS treatment was unexpected. Levels of soluble IL-6 protein in the culture medium also decreased with decreasing levels of LPS over 24 h.
Keywords: Cytokines; Early endosomes; Schwann cells; Toll-like receptor 4; Transforming factors.