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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. - Highlights: • Antigen-induced IL-6 and IL-13 production was augmented by acidic pH in mast cells. • Acidic pH-induced actions were associated with activation of p38 MAPK and Akt. • Inhibition ofmore » p38 MAPK and Akt attenuated cytokine responses to acidic pH. • Acidic pH effects are not attributable to actions of known proton-sensing GPCRs.« less

Authors:
 [1];  [2];  [3];  [4];  [1];  [2]; ;  [4];  [5]; ; ;  [1];  [4];  [1];  [6];  [1];  [4]
  1. Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi (Japan)
  2. (Japan)
  3. Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)
  4. Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan)
  5. Department of Anatomy, Graduate School of Medicine, Teikyo University, Tokyo (Japan)
  6. Gunma University Graduate School of Health Sciences, Maebashi (Japan)
Publication Date:
OSTI Identifier:
22462232
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 464; Journal Issue: 3; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACIDIFICATION; ALBUMINS; ANTIGENS; BLOOD SERUM; BONE MARROW; DINITROPHENOL; ENVIRONMENT; INFLAMMATION; INHIBITION; MAST CELLS; MICE; MUCOUS MEMBRANES; PH VALUE; PROTONS; SKIN; SURFACES

Citation Formats

Kamide, Yosuke, E-mail: m08702012@gunma-u.ac.jp, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Ishizuka, Tamotsu, Tobo, Masayuki, Tsurumaki, Hiroaki, Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Aoki, Haruka, Mogi, Chihiro, Nakakura, Takashi, Yatomi, Masakiyo, Ono, Akihiro, Koga, Yasuhiko, Sato, Koichi, Hisada, Takeshi, Dobashi, Kunio, Yamada, Masanobu, and Okajima, Fumikazu. Acidic environment augments FcεRI-mediated production of IL-6 and IL-13 in mast cells. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.07.077.
Kamide, Yosuke, E-mail: m08702012@gunma-u.ac.jp, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Ishizuka, Tamotsu, Tobo, Masayuki, Tsurumaki, Hiroaki, Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Aoki, Haruka, Mogi, Chihiro, Nakakura, Takashi, Yatomi, Masakiyo, Ono, Akihiro, Koga, Yasuhiko, Sato, Koichi, Hisada, Takeshi, Dobashi, Kunio, Yamada, Masanobu, & Okajima, Fumikazu. Acidic environment augments FcεRI-mediated production of IL-6 and IL-13 in mast cells. United States. doi:10.1016/J.BBRC.2015.07.077.
Kamide, Yosuke, E-mail: m08702012@gunma-u.ac.jp, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Ishizuka, Tamotsu, Tobo, Masayuki, Tsurumaki, Hiroaki, Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Aoki, Haruka, Mogi, Chihiro, Nakakura, Takashi, Yatomi, Masakiyo, Ono, Akihiro, Koga, Yasuhiko, Sato, Koichi, Hisada, Takeshi, Dobashi, Kunio, Yamada, Masanobu, and Okajima, Fumikazu. Fri . "Acidic environment augments FcεRI-mediated production of IL-6 and IL-13 in mast cells". United States. doi:10.1016/J.BBRC.2015.07.077.
@article{osti_22462232,
title = {Acidic environment augments FcεRI-mediated production of IL-6 and IL-13 in mast cells},
author = {Kamide, Yosuke, E-mail: m08702012@gunma-u.ac.jp and Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara and Ishizuka, Tamotsu and Tobo, Masayuki and Tsurumaki, Hiroaki and Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi and Aoki, Haruka and Mogi, Chihiro and Nakakura, Takashi and Yatomi, Masakiyo and Ono, Akihiro and Koga, Yasuhiko and Sato, Koichi and Hisada, Takeshi and Dobashi, Kunio and Yamada, Masanobu and Okajima, Fumikazu},
abstractNote = {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. - Highlights: • Antigen-induced IL-6 and IL-13 production was augmented by acidic pH in mast cells. • Acidic pH-induced actions were associated with activation of p38 MAPK and Akt. • Inhibition of p38 MAPK and Akt attenuated cytokine responses to acidic pH. • Acidic pH effects are not attributable to actions of known proton-sensing GPCRs.},
doi = {10.1016/J.BBRC.2015.07.077},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 464,
place = {United States},
year = {Fri Aug 28 00:00:00 EDT 2015},
month = {Fri Aug 28 00:00:00 EDT 2015}
}
  • Highlights: • We studied the interaction between tumor cells and fibroblasts in ameloblastoma. • AM-3 ameloblastoma cells secreted significantly high IL-1α levels. • IL-1α derived from AM-3 cells promoted IL-6 and IL-8 secretion of fibroblasts. • IL-6 and IL-8 activated the cellular motility and proliferation of AM-3 cells. - Abstract: Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactionsmore » are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave interactively via these cytokines to create a microenvironment that leads to the extension of ameloblastomas.« less
  • Local acidosis is one of the characteristic features of the cancer microenvironment. Many reports indicate that acidosis accelerates the proliferation and invasiveness of cancer cells. However, whether acidic conditions affect lymphatic metastasis is currently unknown. In the present study, we focused on the effects of acidosis on lymphatic endothelial cells (LECs) to assess the relationship between acidic microenvironments and lymph node metastasis. We demonstrated that normal human LECs express various acid receptors by immunohistochemistry and reverse transcriptase-polymerase chain reaction (PCR). Acidic stimulation with low pH medium induced morphological changes in LECs to a spindle shape, and significantly promoted cellular growthmore » and tube formation. Moreover, real-time PCR revealed that acidic conditions increased the mRNA expression of interleukin (IL)-8. Acidic stimulation increased IL-8 production in LECs, whereas a selective transient receptor potential vanilloid subtype 1 (TRPV1) antagonist, 5′-iodoresiniferatoxin, decreased IL-8 production. IL-8 accelerated the proliferation of LECs, and inhibition of IL-8 diminished tube formation and cell migration. In addition, phosphorylation of nuclear factor (NF)-κB was induced by acidic conditions, and inhibition of NF-κB activation reduced acid-induced IL-8 expression. These results suggest that acidic microenvironments in tumors induce lymphangiogenesis via TRPV1 activation in LECs, which in turn may promote lymphatic metastasis. - Highlights: • Acidity accelerates the growth, migration, and tube formation of LECs. • Acidic condition induces IL-8 expression in LECs. • IL-8 is critical for the changes of LECs. • IL-8 expression is induced via TRPV1 activation.« less
  • Toll-like receptor 4 (TLR4) is important in promoting inflammation and vascular smooth muscle cell (VSMC) migration, both of which contribute to atherosclerosis development and progression. But the mechanism underlying the regulation of TLR4 in VSMC migration remains unclear. Stimulation of VSMCs with LPS increased the cellular level of F-spondin which is associated with the regulation of proinflammatory cytokine production. The LPS-induced F-spondin expression depended on TLR4-mediated PI3K/Akt pathway. Suppression of F-spondin level by siRNA inhibited not only F-spondin expression but also LPS-induced phosphorylation of cAMP response element binding protein (CREB) and IL-6 expression, VSMC migration and proliferation as well asmore » MMP9 expression. Moreover, suppression of CREB level by siRNA inhibited TLR4-induced IL-6 production and VSMC migration. Inhibition of F-spondin siRNA on LPS-induced migration was restored by addition of exogenous recombinant mouse IL-6. We conclude that upon ligand binding, TLR4 activates PI3K/Akt signaling to induce F-spondin expression, subsequently control CREB-mediated IL-6 production to promote VSMC migration. These findings provide vital insights into the essential role of F-spondin in VSMC function and will be valuable for developing new therapeutic strategies against atherosclerosis. -- Highlights: •LPS-induced F-spondin expression of VSMCs is via a TLR4/PI3K/Akt signaling. •F-spondin is pivotal for LPS-induced CREB-mediated IL-6 production. •F-spondin is required for LPS-induced VSMC migration and proliferation.« less
  • Highlights: ► 15d-PGJ{sub 2} decreased IL-13 mRNA transcription and secretion in activated T cells. ► IL-13 inhibition by 15d-PGJ{sub 2} is independent of PPAR-γ. ► The nuclear factor-κB mediates the 15d-PGJ{sub 2}-dependent down regulation of IL-13. -- Abstract: Interleukin (IL)-13 is a cytokine produced by activated CD4{sup +} T cells that plays a critical role in promoting allergic responses and tumor cell growth. The 15-deoxy-Δ{sup 12,14}-prostaglandin J{sub 2} (15d-PGJ{sub 2}) is a natural ligand for the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ), a known regulator of anti-inflammatory activities. We determined the effects of 15d-PGJ{sub 2} on IL-13 expression inmore » the Jurkat E6.1 T-cell line and in peripheral blood mononuclear cells. Semi-quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay revealed that treatment of activated T cells with 15d-PGJ{sub 2} significantly decreased IL-13 mRNA transcription and secretion, respectively. This inhibition by 15d-PGJ{sub 2} was independent of PPAR-γ since treatment with GW9662, an irreversible antagonist of the nuclear receptor, produced no effect. Our data also revealed the involvement of nuclear factor-κB in mediating 15d-PGJ{sub 2}-dependent down regulation of IL-13 expression. Collectively, these results demonstrate the potential of 15d-PGJ{sub 2} in attenuating expression and production of IL-13 in activated T cells.« less
  • The uptake of low density lipoprotein (LDL) by cultured mouse macrophages was markedly promoted by isolated rat mast cell granules present in the culture medium. The granule-mediated uptake of /sup 125/I-LDL enhanced the rate of cholesteryl ester synthesis in the macrophages, the result being accumulation of cholesteryl esters in these cells. Binding of LDL to the granules was essential for the granule-mediated uptake of LDL by macrophages, for the uptake process was prevented by treating the granules with avidin or protamine chloride or by treating LDL with 1,2-cyclohexanedione, all of which inhibit the binding of LDL to the granules. Inhibitionmore » of granule phagocytosis by the macrophages with cytochalasin B also abolished the granule-mediated uptake of LDL. Finally, mouse macrophage monolayers and LDL were incubated in the presence of isolated rat serosal mast cells. Stimulation of the mast cells with compound 48/80, a degranulating agent, resulted in dose-dependent release of secretory granules from the mast cells and a parallel increase in /sup 14/C cholesteryl ester synthesis in the macrophages. The results show that, in this in vitro model, the sequence of events leading to accumulation of cholesteryl esters in macrophages involves initial stimulation of mast cells, subsequent release of their secretory granules, binding of LDL to the exocytosed granules, and, finally, phagocytosis of the LDL-containing granules by macrophages.« less