Received: 19 September 2018 | Accepted: 15 October 2018 DOI: 10.1002/jcp.27698 MINI ‐ REVIEW Melatonin, a toll‐like receptor inhibitor: Current status and future perspectives Omid Reza Tamtaji 1,2 | Moein Mobini 3 | Russel J. Reiter 4 | Abolfazl Azami 5 | Mohammad Saeed Gholami 6,7 | Zatollah Asemi 8 1 Halal Research Center of IRI, FDA, Tehran, Iran 2 Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran 3 Kinesiology Department, University of Calgary, Calgary, Alberta, Canada 4 Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 5 Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran 6 Skull Base Research Center, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran 7 Student Research Committee, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran 8 Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran Correspondence Zatollah Asemi, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan 8715988141, Iran. Email: asemi_r@yahoo.com Abstract Toll‐like receptors (TLRs) are crucial activators of inflammatory responses, they are considered immune receptors. TLRs are of fundamental importance in the pathophysiology of disorders related to inflammation including neurodegenerative diseases and cancer. Melatonin is a beneficial agent in the treatment of inflammatory and immune disorders. Melatonin is potent anti‐inflammatory hormone that regulates various molecular pathways. Withal, limited studies have evaluated the inhibitory role of melatonin on TLRs. This review summarizes the current knowledge related to the effects of melatonin on TLRs in some common inflammatory and immunity disorders. KEYWORDS inflammation, melatonin, myeloid differentiation factor 88, toll‐like receptor 1 | INTRODUCTION Toll‐like receptors (TLRs) are an essential part of the innate immune system; they are activated in response to inflammation. The TLR family consists 10 members (TLR1–TLR10) in humans and 12 (TLR1–TLR9, TLR11–TLR13) in mice. TLRs are localized to the cell surface and on the intracellular compartments such as the ER, endosome, lysosome, or endolysosome (Botos, Segal, & Davies, 2011). TLRs are classified into two general categories based on their localization, cell surface TLRs and intracellular TLRs. Cell surface TLRs include: TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10, whereas intracellular TLRs which are associated with the endosome include: TLR3, TLR7, TLR8, TLR9, TLR11, TLR12, and TLR13 (Iwasaki & Medzhitov, 2004; Kawai & Akira, 2010). A wide range of TLRs are expressed within the central nervous system (CNS), especially in microglia as well as in most cells and organs (Begon et al., 2007; Bsibsi, Ravid, Gveric, & Van Noort, 2002; Cervantes et al., 2011; Seya, Funami, Taniguchi, & Matsumoto, 2005). The microglia express messenger RNA (mRNA) for TLRs 1–9, whereas astrocytes mostly express TLR3, low‐level TLR1, TLR4, TLR5, and TLR9, and rare‐to‐undetectable TLR2, TLR6, TLR7, TLR8, and TLR10 mRNA. Activation of innate immune responses in the CNS is not homogeneous but rather specific to the cell type and environmental signals (Jack et al., 2005). TLR stimulation promotes J Cell Physiol. 2018;1–8. wileyonlinelibrary.com/journal/jcp © 2018 Wiley Periodicals, Inc. | 1