The Effects of Neuronal Growth Factors on LPS-Activated Schwann Cells

Schwann cells (SCs) are the principal support cells of neurons in the peripheral nervous system, that both myelinate axons for the rapid conduction of electrical impulses as well as assist in axonal repair during nerve injury. During nerve injury, SCs secrete tumor necrosis factor alpha (TNF-α)1,5,6 and other proinflammatory mediators1,6, attracting macrophages to the site of injury to induce inflammation and clear myelin debris.1,6 Once the debris is cleared, the neuron stimulates SC proliferation by secreting neuronal mitogens, such as heregulin3,4, and an unknown factor that activates the cAMP pathway3, an important regulator of cell division.3,4 In vitro, SCs can be treated with an artificial plant extract called forskolin3,4 to activate the cAMP pathway. Studies show that heregulin and forskolin act synergistically to enhance SC proliferation under normal, non-inflammatory conditions.4 Although the role of cAMP in proliferation and axonal regeneration is well-known, not much has been explored about its function in SCs during nerve injury and inflammation. In vitro, inflammatory conditions can be simulated by treating SCs with lipopolysaccharide (LPS), a cell-wall immunostimulatory component of Gram-negative bacteria.1,2,6 In most mammalian cells, LPS binds to a transmembrane protein called toll-like receptor 4 (TLR4)1,2,6, activating both the mitogen-activated protein kinase (MAPK) pathway1,2,6 and the nuclear factor kappa B (NF-κB) pathway2,6, to promote the secretion of inflammatory mediators, such as TNF-α.1,2,6 With that being said, the aim of this preliminary study was to determine the role of the cAMP pathway in SCs during LPS-induced inflammation. It was hypothesized that SCs stimulated with LPS and growth factors will have higher proliferation than SCs treated with LPS only.https://digitalcommons.misericordia.edu/research_posters2022/1004/thumbnail.jp