tretinoin and Behcet-Syndrome

Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet's disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD.

Topics: Adult; Algeria; Antineoplastic Agents; Behcet Syndrome; Down-Regulation; Female; Humans; Leukocytes, Mononuclear; Male; NF-kappa B; Nitric Oxide; Tretinoin

Behçet's disease (BD) and systemic lupus erythematosus (SLE) are two autoimmune inflammatory diseases of indefinite etiology. However, up till now, no study has explored the exact regulatory mechanisms of lncRNA maternally expressed gene-3 (MEG3) over the balance between regulatory T-cells (Treg) and T helper-17 (Th17) cells in BD and SLE.. The current study aimed to investigate the role of lncRNA MEG3 in the interplay between the anti-inflammatory Treg/transcription factor forkhead box P3 (FOXP3) axis versus the pro-inflammatory Th17/retinoic acid orphan receptor-γt (RORγt) axis.. 100 subjects, 35 with BD and 35 with SLE in addition to 30 healthy participants were included in the study. Gene expression analysis was performed and ShinyGO database was utilized for in-depth analysis and graphical visualization of the gene ontology (GO) and pathway enrichment analysis for lncRNA and the other target genes.. The current results demonstrate the upregulation of lncRNA MEG3 in BD but not SLE patients. Moreover, significant differences in RORγt and FOXP3 were found between BD and SLE patients. The present findings linked lncRNA MEG3 to BD activity scores as well as CRP levels. Finally, lncRNA MEG3 showed excellent diagnostic power for BD, in addition to adequate discriminative power that can be used to differentiate between BD and SLE.. The current study objectively elucidated a framework for the involvement of Treg/Th17 through transcription factors RORγt and FOXP3, in addition to their links to the downstream cytokines network including TGF-ꞵ, IL-10, IL-17 and IL-23 in BD and SLE pathogenesis and activity.

Topics: Anti-Inflammatory Agents; Behcet Syndrome; Forkhead Transcription Factors; Humans; Interleukin-10; Interleukin-17; Interleukin-23; Lupus Erythematosus, Systemic; Nuclear Receptor Subfamily 1, Group F, Member 3; RNA, Long Noncoding; T-Lymphocytes, Regulatory; Th17 Cells; Tretinoin