Potential role of melatonin in autoimmune diseases. (August 2019)

• Record Type: Journal Article
• Authors: Zhao, Chan-Na; Wang, Peng; Mao, Yan-Mei; Dan, Yi-Lin; Wu, Qian; Li, Xiao-Mei; Wang, De-Guang; Davis, Callan; Hu, Wenbiao; Pan, Hai-Feng
• Is Part Of: Cytokine & growth factor reviews. Volume 48(2019)
• Page Start: 1
• Page End: 10
• Publication Date: 2019-08
• Subjects: AANAT Arylalkylamine N-acetyltransferase -- AMT Acetyl-melatonin -- AOPP advanced oxidation protein products -- AS Ankylosing spondylitis -- BAFF B-cell-activating factor of TNF family -- BASDAI Bath ankylosing spondylitis disease activity index -- BMT Benzoyl-melatonin -- CAMKIV calcium/calmodulindependent kinase IV -- CRP C-reactive protein -- EAE experimental autoimmune encephalomyelitis -- ERK Extracellular signal regulated kinase -- ESR Erythrocyte sedimentation rate -- GAD antibody Glutamic acid decarboxylase antibody -- GI Gastrointestinal line -- GPx Glutathione peroxide -- GSH Glutathione -- HIOMT Hydroxyndole-O-methytransferase -- HIS 5-hydroxy-2'-isobutyl-streptochlorin -- HO-1 heme oxygenase‐1 -- IBD Inflammatory bowel disease -- ICA antibody Islet cell antibody -- IL Interleukin -- MAPK mitogen-activated protein kinase -- MDA Malondialdehyde -- MLT Melatonin -- MNs myenteric neurons -- MPO Myeloperoxidase -- MS Multiple sclerosis -- MSH Melanocyte stimulating hormone -- MSFC MS functional composite score -- MT1 MLT membrane receptors type 1 -- MT2 MLT membrane receptors type 2 -- MT3 MLT binds to the quinone reductase enzyme family -- MTNRIB MLT receptor type 1B -- MSFC Multiple sclerosis functional composite score -- MyD 88 myeloid differentiation factor 88 -- NAA N-acetylaspartate -- NAT N-acetyltransferase -- NF-κB Nuclear transcription factor kappa B -- NK Natural killer -- NO Nitric oxide -- NOS Nitric oxide synthase -- Nrf2 nuclear erythroid 2-related factor 2 -- PBMCs Peripheral blood mononuclear cells -- PDC pyruvate dehydrogenase complex -- PDK4 pyruvate dehydrogenase kinase-4 -- RA Rheumatoid arthritis -- RF Rheumatoid factor -- RORα/RZR Retinoid-related orphan nuclear hormone receptor -- ROS free radicals of oxygen species -- RRMS relapsing-remitting multiple sclerosis -- SLE Systemic lupus erythematosus -- SLEDAI Systemic lupus erythematosus disease activity index -- 6-SMT 6-sulphatoxymelatonin -- SNP Single-nucleotide polymorphism -- SOD Superoxide dismutase -- SSc Systemic sclerosis -- TAC Total antioxidant capacity -- T1DM Type 1 diabetes mellitus -- Th1 T helper 1 -- TLRs toll like receptors -- TNF-α Tumor Necrosis Factor-α -- Tregs Regulatory T cells -- Tr1 type 1 regulatory -- TOS Total oxidant status -- TPH Tryptophan hydroxylases -- UC Ulcerative colitis; Melatonin -- Autoimmunity -- Autoimmune diseases -- Systemic lupus erythematosus -- Rheumatoid arthritis; Cytokines -- Periodicals; 571.84
• DOI: 10.1016/j.cytogfr.2019.07.002
• Languages: English
• ISSNs: 1359-6101

Abstract

Graphical abstract: Highlights: MLT boosts Tr1 cell differentiation and suppresses Th17 cell differentiation. MLT can reduce the apoptosis of cells through decreasing the expression of Bax and preventing the loss of Bcl-2 proteins. MLT can regulate immune response through Nrf2, NFIL3, BAFF, and NF-κB. MLT may regulate the expression of microRNAs and other non-coding RNAs, ultimately alleviating autoimmune diseases Abstract: Autoimmune diseases are a broad spectrum of disorders involved in the imbalance of T-cell subsets, in which interplay or interaction of Th1, Th17 and Tregs are most important, resulting in prolonged inflammation and subsequent tissue damage. Pathogenic Th1 and Th17 cells can secrete signature proinflammatory cytokines, including interferon (IFN)-γ and IL-17, however Tregs can suppress effector cells and dampen a wide spectrum of immune responses. Melatonin (MLT) can regulate the humoral and cellular immune responses, as well as cell proliferation and immune mediators. Treatment with MLT directly interferes with T cell differentiation, controls the balance between pathogenic and regulatory T cells and regulates inflammatory cytokine release. MLT can promote the differentiation of type 1 regulatory T cells via extracellular signal regulated kinase 1/2 (Erk1/2) and retinoic acid-related orphan receptor-α (ROR-α) and suppress the differentiation of Th17 cells via the inhibition of ROR-γt and ROR-α expression through NFIL3. Moreover, MLT inhibits NF-κB signaling pathway to reduce TNF-α and IL-1β expression, promotes Nrf2 gene and protein expression to reduce oxidative and inflammatory states and regulates Bax and Bcl-2 to reduce apoptosis; all of which alleviate the development of autoimmune diseases. Thus, MLT can serve as a potential new therapeutic target, creating opportunities for the treatment of autoimmune diseases. This review aims to highlight recent advances in the role of MLT in several autoimmune diseases with particular focus given to novel signaling pathways involved in Th17 and Tregs as well as cell proliferation and apoptosis.