Background: Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, characterized by inflammation, demyelination, and neurodegeneration. Experimental autoimmune encephalomyelitis (EAE) is a well-established preclinical model for examining MS pathophysiology. Peptide inhibitor of transendothelial migration (PEPITEM) is an immunomodulatory peptide; however, its effects on gene expression in EAE remain insufficiently characterized. In this study, we aimed to evaluate the immunomodulatory effects of PEPITEM in EAE by comparing therapeutic (postinduction) and prophylactic (preinduction) administration using RT2 Profiler™ PCR Array–based gene expression analysis. Methods: Ten female C57BL/6 mice aged 9–13 weeks (body weight, 21 ± 3 g) were induced with EAE and assigned to four experimental groups: G1 (EAE + scramble peptide), G2 (EAE + PEPITEM), G3 (EAE + scramble peptide administered preinduction), and G4 (EAE + PEPITEM administered preinduction). Gene expression was assessed using RT2 Profiler™ PCR Arrays, with fold regulation calculated for each gene. Results: PEPITEM exerted distinct, time-dependent effects on immune gene expression. Therapeutic administration (G2 vs. G1) resulted in broad upregulation of immune-related genes, with notable increases in motif chemokine ligand 11 (Cxcl11) (30.14-fold), Cd28 (3.83-fold), and Cd40 (3.81-fold), consistent with enhanced expression of genes associated with T-cell costimulation, cytokine signaling, and chemokine signaling. Conversely, prophylactic administration (G4 vs. G3) produced marked suppression of inflammatory gene expression, with 33 of 34 genes downregulated. The most strongly suppressed genes were motif chemokine ligand 10 (Cxcl10) (–17.11-fold), interferon-gamma (Ifng) (–13.12-fold), and tumor necrosis factor-alpha (Tnf) (–12.43-fold), indicating reduced expression of genes involved in chemokine signaling and T-cell migration. Conclusion: PEPITEM modulates immune-related gene expression in EAE in a timing-dependent manner. Its opposing effects—gene expression activation postinduction and suppression preinduction—suggest context-specific immunomodulatory properties that may be relevant to therapeutic strategies for MS.
Alassiri et al. (Thu,) studied this question.