The Role of Schwann Cells in Nerve Injury: Forskolin-Mediated cAMP Activation Upregulates TNFα Expression Despite NF-κB Downregulation in LPS-Treated Schwann Cells

Although Schwann cells are known to play a role in axonal regeneration following nerve injury and inflammation, the exact mechanism is unknown. This study explores two potential mechanisms: the NF-κB and cAMP pathways. The NF-κB pathway produces cytokines, such as TNFα, to regulate inflammation, whereas the cAMP pathway is anti-inflammatory and regulates Schwann cell proliferation via AKAP95 and cyclin D3. Although it is well-known that NF-κB and cAMP are involved in inflammation, not much is known regarding the effects of forskolin-mediated cAMP activation on LPS-mediated NF-κB activation in Schwann cells. In this study, RT4-D6P2T immortalized rat Schwann cells were treated with 0.1, 1, or 10 μg/mL of LPS, with or without 2 μM of forskolin, for 3 hours, and then an MTT viability assay and Western blot were performed. It was found that cAMP activation decreased cell viability regardless of LPS dose compared to the control. It was also found that at high doses of LPS, cAMP activation upregulated TNFα expression despite a downregulation of NF-κB, meaning cAMP may regulate TNFα through NF-κB-independent mechanisms. Furthermore, at high doses of LPS, cAMP activation downregulated AKAP95 and cyclin D3 expression and decreased cell viability, meaning that at high LPS doses, NF-κB might inhibit cAMP\u27s ability to upregulate AKAP95 and cyclin D3, decreasing cell proliferation and thus viability. A better understanding of the potential interactions between the NF-κB and cAMP pathways in Schwann cells may help to find a potential therapeutic target for the treatment of nerve injury and inflammation.https://digitalcommons.misericordia.edu/research_posters2023/1029/thumbnail.jp