title: Sulforaphane regulates phenotypic and functional switching of both induced and spontaneously differentiating human monocytes.
abstract: At the site of inflammation, switching default on polarization of monocyte differentiation into classically activated macrophages (M1 type) is one of the pathogenic outcomes in several inflammatory autoimmune diseases, such as rheumatoid arthritis and osteoarthritis. In rheumatoid and osteoarthritis, a soluble collagen known as self-antigen is considered as a biomarker and acts as an important inflammatory mediator. In the present study, we investigated the effects of sulforaphane (SFN) on phenotypic changes and functional switching during in vitro induced and spontaneous differentiation of monocytes/macrophages, whose conditions were established with THP1 induced by PMA, and human peripheral blood monocytes, respectively. SFN at non-cytotoxic concentration (10μM) blocked soluble collagen induced inflammatory responses specific to M1 macrophages, COX-2, iNOS, surface CD14, CD197 expressions and production of IL12p70, suggesting that signals induced by SFN eventually shifted macrophage polarization to a direction specific to M2 macrophages (CD36high CD197extremely low). Results obtained with the induction of inflammatory conditions specific to M1 macrophages followed by SFN treatment showed that MAPKs were involved in the M1 to M2 phenotype switching. This immune-modulatory nature of SFN provides a clear indication for its ability to alleviate chronic inflammatory diseases by targeting monocytes/macrophages.
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER), PO Bhimpur-Padanpur, Via Jatni, Khurda 752050, India.
authors.forename: Sanjima
authors.initials: S
authors.lastname: Pal
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER), PO Bhimpur-Padanpur, Via Jatni, Khurda 752050, India. Electronic address: badireenath@niser.ac.in.
authors.forename: V Badireenath
authors.initials: VB
authors.lastname: Konkimalla
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D010003:Osteoarthritis / Q000188:drug therapy*; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects; D013454:Sulfoxides
chemical_list: D000893:Anti-Inflammatory Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D018664:Interleukin-12; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; C016766:sulforaphane
keywords: Autoimmune diseases; Collagen; Immune suppression; Inflammation; M1/M2 macrophages; Sulforaphane