transforming-growth-factor-alpha and Multiple-Sclerosis

To evaluate the aryl hydrocarbon receptor (AHR)-dependent transforming growth factor alpha (TGF-α)/vascular endothelial growth factor B (VEGF-B) ratio, which regulates the effects of metabolic, dietary, and microbial factors on acute and chronic CNS inflammation, as a potential marker in multiple sclerosis (MS).. TGF-α, VEGF-B, and AHR agonistic activity were determined in serum of 252 patients with relapsing-remitting (RR) MS, primary and secondary progressive MS, as well as during active disease (clinically isolated syndrome [CIS] and RRMS relapse).. The TGF-α/VEGF-B ratio and AHR agonistic activity were decreased in all MS subgroups with a stable disease course as compared to controls. During active CNS inflammation in CIS and RRMS relapse, the TGF-α/VEGF-B ratio and AHR agonistic activity were increased. Conversely, in patients with minimal clinical impairment despite long-standing disease, the TGF-α/VEGF-B ratio and AHR agonistic activity were unaltered. Finally, the TGF-α/VEGF-B ratio and AHR agonistic activity correlated with neurologic impairment and time to conversion from CIS to MS.. The AHR-dependent TGF-α/VEGF-B ratio is altered in a subtype, severity, and disease activity-specific manner and correlates with time to conversion from CIS to MS. It may thus represent a novel marker and serve as additive guideline for immunomodulatory strategies in MS.. This study provides Class III evidence that serum levels of AHR, TGF-α, and VEGF-B distinguish subtypes of MS and predict the severity and disease activity of MS.

Topics: Adult; Humans; Male; Middle Aged; Multiple Sclerosis; Patient Acuity; Prognosis; Receptors, Aryl Hydrocarbon; Transforming Growth Factor alpha; Vascular Endothelial Growth Factor B

Microglia and astrocytes modulate inflammation and neurodegeneration in the central nervous system (CNS)

Topics: Animals; Astrocytes; Cells, Cultured; Central Nervous System; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; ErbB Receptors; Female; Humans; Inflammation; Lipopolysaccharide Receptors; Mice; Mice, Inbred C57BL; Microglia; Multiple Sclerosis; Receptors, Aryl Hydrocarbon; Symbiosis; Transforming Growth Factor alpha; Tryptophan; Vascular Endothelial Growth Factor B; Vascular Endothelial Growth Factor Receptor-1

Topics: Animals; Astrocytes; Bacteria; Brain; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Gastrointestinal Microbiome; Humans; Mice; Microglia; Multiple Sclerosis; Receptor Cross-Talk; Transforming Growth Factor alpha; Vascular Endothelial Growth Factor B

Immunochemical monitoring was used to examine 37 patients with remittent multiple sclerosis (MS) for 3 years. There were changes in the blood concentrations of the supernatants IL-1 beta, IL-2, IL-6, alpha-TNF, in the serum levels of the adhesion molecule sVCAM, the neurospecific proteins GFAP and alpha 2GP. Only does active MS show a simultaneous increase in the serum concentrations of SVCAM and GFAP and alpha 2GP, which may be used as a test for the objectification of MS aggravation, the efficiency of therapy. The revealed higher secretion of antiinflammatory of cytokines at all disease stages, no recovery of blood-brain barrier responsiveness and at remission provide evidence for the likelihood of a permanent immunopathological process in MS with prevailing inflammatory and destructive changes during a clinical exacerbation and of the induction of active astrogliosis at its remission.

Topics: Adolescent; Adult; Biomarkers; Blood-Brain Barrier; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Glial Fibrillary Acidic Protein; Humans; Interleukins; Male; Middle Aged; Multiple Sclerosis; Recurrence; Transforming Growth Factor alpha; Vascular Cell Adhesion Molecule-1