Staphylococcus aureus peptidoglycan stimulates granulocyte macrophage colony-stimulating factor production from human epidermal keratinocytes via mitogen-activated protein kinases.
Epidermal keratinocytes with atopic dermatitis (AD) overproduce mediators such as granulocyte macrophage colony-stimulating factor (GM-CSF), which are associated with pathology of AD. We found that peptidoglycan (PGN) of Staphylococcus aureus, which is frequently observed in lesion with AD, induced the production of numerous mediators such as GM-CSF and regulated on activation, normal T-cell expressed and secreted. Moreover, PGN phosphorylated extracellular-signal-regulated kinases and p38 mitogen-activated protein kinase, which were involved in the induction of GM-CSF expression. These results suggested that PGN of S. aureus directly exacerbates inflammation of inflammatory skin disease.
Matsubara
Masahiro
M
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan. masahiro.matsubara@kyowa.co.jp
Harada
Daisuke
D
Manabe
Haruhiko
H
Hasegawa
Kazuhide
K
D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000078404:Epidermal Cells; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010457:Peptidoglycan / Q000494:pharmacology*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000737:chemistry*; D051193:Toll-Like Receptors
D018946:Chemokine CCL5; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D008562:Membrane Glycoproteins; D010457:Peptidoglycan; D011725:Pyridines; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one