The p38 mitogen-activated protein kinases modulate endothelial cell survival and tissue repair

Nobuhiro Kanaji, Amy Nelson, Diane S. Allen-Gipson, Tadashi Sato, Masanori Nakanishi, Xingqi Wang, Yingji Li, Hesham Basma, Joel Michalski, Maha Farid, Stephen I. Rennard, Xiangde Liu

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Objective and design: This study is designed to investigate the role of p38 MAPK in modulating human pulmonary artery endothelial cells (HPAECs) survival and tissue repair functions. Methods: HPAECs (passage 8-12) were used for all experiments. Cells were treated with IL-1β (0.5 or 2 ng/ml) or p38 inhibitor (SB203580 or SB220025, 5 μM each). Cells were also transfected with 50 nM siRNAs. Cell length was measured using ImageJ software. Collagen gel contraction and wound close assay were performed to evaluate tissue repair functions. Results: IL-1β activated p38 MAPK and induced morphologic change of HPAECs. The p38 inhibitors further augmented IL-1β-induced cell morphologic change, prevented cell death, and augmented collagen gel contraction. Suppression of p38α, γ, or δ, but not p38β resulted in cell morphologic alteration, and suppressing any one of p38 isoforms by siRNAs increased cell survival. Suppression of p38α or δ augmented gel contraction. While p38α suppression stimulated cell migration, suppressing the rest of three isoforms inhibit cell migration. Nuclear factor p65-siRNA blocked IL-1β-induced cell morphologic change, but did not affect p38 inhibitor-induced change. Conclusion: These findings suggest that p38 MAPK may negatively modulate tissue repair functions of endothelial cells via p65 independent pathway.

Original languageEnglish (US)
Pages (from-to)233-244
Number of pages12
JournalInflammation Research
Volume61
Issue number3
DOIs
StatePublished - Mar 1 2012

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Keywords

  • Apoptosis
  • Endothelial cells
  • Interleukin-1
  • Repair
  • p38

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

Kanaji, N., Nelson, A., Allen-Gipson, D. S., Sato, T., Nakanishi, M., Wang, X., Li, Y., Basma, H., Michalski, J., Farid, M., Rennard, S. I., & Liu, X. (2012). The p38 mitogen-activated protein kinases modulate endothelial cell survival and tissue repair. Inflammation Research, 61(3), 233-244. https://doi.org/10.1007/s00011-011-0405-7