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

Inflammation Research

, Volume 61, Issue 3, pp 233–244 | Cite as

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
Original Research Paper

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.

Keywords

p38 Interleukin-1 Endothelial cells Repair Apoptosis 

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Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  • Nobuhiro Kanaji
    • 1
    • 2
  • Amy Nelson
    • 2
  • Diane S. Allen-Gipson
    • 2
  • Tadashi Sato
    • 3
  • Masanori Nakanishi
    • 4
  • Xingqi Wang
    • 2
  • YingJi Li
    • 5
  • Hesham Basma
    • 2
  • Joel Michalski
    • 2
  • Maha Farid
    • 2
  • Stephen I. Rennard
    • 2
  • Xiangde Liu
    • 2
  1. 1.Division of Endocrinology and Metabolism, Hematology, Rheumatology and Respiratory MedicineKagawa UniversityKagawaJapan
  2. 2.Pulmonary, Critical Care, Sleep and Allergy DivisionUniversity of Nebraska Medical CenterOmahaUSA
  3. 3.Department of Respiratory MedicineJuntendo University School of MedicineTokyoJapan
  4. 4.Third Department of Internal MedicineWakayama Medical University School of MedicineWakayamaJapan
  5. 5.Department of Hygiene and Public HealthNippon Medical SchoolTokyoJapan

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