Involvement of Nrf2-mediated heme oxygenase-1 expression in anti-inflammatory action of chitosan oligosaccharides through MAPK activation in murine macrophages.
Chitosan and its derivatives have been reported to have anti-inflammatory effects in vitro and in vivo. It is also suggested that chitosan and its derivatives could be up-regulating heme oxygenase-1 (HO-1) in different models. However, the up-regulation of HO-1 by chitosan oligosaccharides (COS) remains unexplored in regard to anti-inflammatory action in lipopolysaccharide (LPS)-stimulated murine macrophages (RAW264.7 cells). Treatment with COS induced HO-1 expression in LPS-stimulated RAW264.7 cells, whereas the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was decreased. Pretreatment with ZnPP, a HO-1 inhibitor, reduced the COS-mediated anti-inflammatory action. HO-1 induction is mediated by activating the nuclear translocation of NF-E2-related factor 2 (Nrf2) using COS. Moreover, COS increased the phosphorylation of extracellular signal regulated kinase (ERK1/2), c-Jun N-terminal kinase/stress-activated protein kinase (JNK), and p38 MAPK. However, specific inhibitors of ERK, JNK, and p38 reduced COS-mediated nuclear translocation of Nrf2. Therefore, HO-1 induction also decreased in RAW264.7 cells. Collectively, COS exert an anti-inflammatory effect through Nrf2/MAPK-mediated HO-1 induction.
Department of Marine-Bio Convergence Science, Pukyong National University, Busan 48547, Republic of Korea.
Jun-Ho
JH
Hyung
Division of Food and Nutrition, Chonnam National University, Gwangju 61186, Republic of Korea.
Chang-Bum
CB
Ahn
Specialized Graduate School of Science & Technology Convergence, Pukyong National University, Busan 48547, Republic of Korea.
Boo
B
Il Kim
Depatment of Ocean Engineering, Pukyong National University, Busan 48513, Republic of Korea.
Kyunghoi
K
Kim
Department of Marine-Bio Convergence Science, Pukyong National University, Busan 48547, Republic of Korea. Electronic address: jjy1915@pknu.ac.kr.
Jae-Young
JY
Je
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D000067996:RAW 264.7 Cells
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D051267:NF-E2-Related Factor 2; D009569:Nitric Oxide; D048271:Chitosan; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases
Anti-inflammatory; Chitosan oligosaccharides; HO-1; MAPKs; Nrf2