title: Acidic environment augments FcεRI-mediated production of IL-6 and IL-13 in mast cells.
abstract: Although blood pH is maintained in a narrow range of around pH 7.4 in living organisms, inflammatory loci are characterized by acidic conditions. Mast cells tend to reside close to the surface of the body in areas such as the mucosa and skin where they may be exposed to exogenous acids, and they play an important role in immune responses. However, little is known about the effects of extracellular acidification on the functions of mast cell. Here, we found that extracellular acidification increased the dinitrophenyl-conjugated human serum albumin (DNP-HSA)-induced production of interleukin (IL)-6 and IL-13 in MC/9 cells or bone marrow-derived mouse mast cells sensitized with anti-DNP IgE. Extracellular acidification also inhibited migration of MC/9 cells toward DNP-HSA. In addition, acidic pH stimulated antigen-induced activation of p38 mitogen-activated protein kinase (MAPK) and protein kinase B (Akt). These findings suggest that extracellular acidification augmented antigen/IgE-induced and FcεRI-mediated production of IL-6 and IL-13 in mast cells, and that this was associated with the enhancement of p38 MAPK and Akt activation.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan; Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Japan. Electronic address: m08702012@gunma-u.ac.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kamide
authors.affiliation: Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Ishizuka
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tobo
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan; Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tsurumaki
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Aoki
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Mogi
authors.affiliation: Department of Anatomy, Graduate School of Medicine, Teikyo University, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakakura
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Yatomi
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ono
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Koga
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hisada
authors.affiliation: Gunma University Graduate School of Health Sciences, Maebashi, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Dobashi
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Okajima
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D004140:Dinitrophenols / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008407:Mast Cells / Q000737:chemistry / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism*; D012709:Serum Albumin / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004140:Dinitrophenols; C517811:GPR4 protein, mouse; D018793:Interleukin-13; D015850:Interleukin-6; D043562:Receptors, G-Protein-Coupled; D017455:Receptors, IgE; D012709:Serum Albumin; C058064:dinitrophenyl-human serum albumin conjugate; D007073:Immunoglobulin E; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Extracellular acidification; IL-13; IL-6; Interleukin; Mast cells; p38 MAPK