title: Heparin inhibits melanosome uptake and inflammatory response coupled with phagocytosis through blocking PI3k/Akt and MEK/ERK signaling pathways in human epidermal keratinocytes.
abstract: To gain insight for the role of mast cell-produced heparin in the regulation of epidermal homeostasis and skin pigmentation, we have investigated the effect of heparin on melanosome uptake and proinflammatory responses in normal human epidermal keratinocytes (NHEKs). We quantified phagocytic activity of NHEKs with uptake of melanosomes or fluorescent microspheres. Heparin exhibited the inhibitory effect on keratinocyte phagocytosis through blocking PI3k/Akt and MEK/ERK signaling pathways. In fact, the heparin-treated NHEKs showed impaired activation of Akt and ERK during phagocytosis, whereas PI3k and MEK inhibitors significantly suppressed melanosome uptake by NHEKs. In addition, the inflammation marker cycloxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2 ) production were induced during phagocytosis, while these effects were downregulated in the presence of heparin. Our observations suggest that heparin may play an antiphagocytic and anti-inflammation role in epidermis of human skin.
authors: Kobe Skin Research Department, Biosignal Research Center, Kobe University, Kobe, Japan.
authors: Chieko
authors: C
authors: Makino-Okamura
authors: Yoko
authors: Y
authors: Niki
authors: Seiji
authors: S
authors: Takeuchi
authors: Chikako
authors: C
authors: Nishigori
authors: Lieve
authors: L
authors: Declercq
authors: Daniel B
authors: DB
authors: Yaroch
authors: Naoaki
authors: N
authors: Saito
mesh_terms: D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D000078404:Epidermal Cells; D005453:Fluorescence; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008543:Melanins / Q000378:metabolism; D020460:Melanosomes / Q000187:drug effects / Q000378:metabolism*; D008863:Microspheres; D010587:Phagocytosis / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008543:Melanins; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D006493:Heparin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D015232:Dinoprostone
keywords: heparin; inflammation; melanosome transfer; phagocytosis