TY - JOUR
T1 - Decreased MCP-1/CCR2 axis-mediated chemotactic effect of conjunctival fibroblasts after transdifferentiation into myofibroblasts
AU - Tsutsumi-Kuroda, Utako
AU - Inoue, Toshihiro
AU - Futakuchi, Akiko
AU - Shobayashi, Kohei
AU - Takahashi, Eri
AU - Kojima, Sachi
AU - Inoue-Mochita, Miyuki
AU - Fujimoto, Tomokazu
AU - Tanihara, Hidenobu
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant numbers 26293375 , 15K15636 , and 26462664 . The sponsor or funding organization had no role in the design or conduct of this research.
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/5
Y1 - 2018/5
N2 - The purpose of this study is to investigate the change in chemotactic effects of human conjunctival fibroblasts (HConFs) after transdifferentiation into myofibroblasts, and to explore related molecular mechanisms. HConFs were treated with 5 ng/mL transforming growth factor (TGF)-β2 for 48 h to induce transdifferentiation into myofibroblasts. The cytokine concentrations in the conditioned media of HConFs were measured by multiplex bead-based immunoassays. The Boyden chamber assay was used to assess the chemotactic effects using the monocyte cell line, THP-1 cells. The concentration of monocyte chemoattractant protein (MCP)-1 in the conditioned media was decreased after transdifferentiation into myofibroblasts (P < 0.001). The conditioned media of HConFs exerted a chemotactic effect on THP-1 cells, but this effect decreased after transdifferentiation into myofibroblasts (P = 0.032). The number of migrated THP-1 cells decreased significantly upon treatment with neutralizing anti-MCP-1 antibodies (P = 0.006) and tended to decrease upon treatment with C-C chemokine receptor (CCR) 2 antagonist. The chemotactic effect of HConFs mediated by the MCP-1/CCR2 axis was decreased after transdifferentiation into myofibroblasts.
AB - The purpose of this study is to investigate the change in chemotactic effects of human conjunctival fibroblasts (HConFs) after transdifferentiation into myofibroblasts, and to explore related molecular mechanisms. HConFs were treated with 5 ng/mL transforming growth factor (TGF)-β2 for 48 h to induce transdifferentiation into myofibroblasts. The cytokine concentrations in the conditioned media of HConFs were measured by multiplex bead-based immunoassays. The Boyden chamber assay was used to assess the chemotactic effects using the monocyte cell line, THP-1 cells. The concentration of monocyte chemoattractant protein (MCP)-1 in the conditioned media was decreased after transdifferentiation into myofibroblasts (P < 0.001). The conditioned media of HConFs exerted a chemotactic effect on THP-1 cells, but this effect decreased after transdifferentiation into myofibroblasts (P = 0.032). The number of migrated THP-1 cells decreased significantly upon treatment with neutralizing anti-MCP-1 antibodies (P = 0.006) and tended to decrease upon treatment with C-C chemokine receptor (CCR) 2 antagonist. The chemotactic effect of HConFs mediated by the MCP-1/CCR2 axis was decreased after transdifferentiation into myofibroblasts.
KW - Chemotaxis
KW - Conjunctival fibroblast
KW - Cytokine
KW - MCP-1
KW - Myofibroblast
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U2 - 10.1016/j.exer.2018.02.008
DO - 10.1016/j.exer.2018.02.008
M3 - Article
C2 - 29458061
AN - SCOPUS:85042383916
SN - 0014-4835
VL - 170
SP - 76
EP - 80
JO - Experimental Eye Research
JF - Experimental Eye Research
ER -