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

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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.

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Acknowledgments

The authors thank Ms. Lillian Richards for the excellent secretarial support of this manuscript. Funding: Larson Endowment, University of Nebraska Medical Center and LB506.

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Hematology, Rheumatology and Respiratory Medicine, Kagawa University, Kagawa, Japan

    Nobuhiro Kanaji

  2. Pulmonary, Critical Care, Sleep and Allergy Division, University of Nebraska Medical Center, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, USA

    Nobuhiro Kanaji, Amy Nelson, Diane S. Allen-Gipson, Xingqi Wang, Hesham Basma, Joel Michalski, Maha Farid, Stephen I. Rennard & Xiangde Liu

  3. Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan

    Tadashi Sato

  4. Third Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan

    Masanori Nakanishi

  5. Department of Hygiene and Public Health, Nippon Medical School, Tokyo, Japan

    YingJi Li

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  1. Nobuhiro Kanaji
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  2. Amy Nelson
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Corresponding author

Correspondence to Xiangde Liu.

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Responsible Editor: Liwu Li.

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Kanaji, N., Nelson, A., Allen-Gipson, D.S. et al. The p38 mitogen-activated protein kinases modulate endothelial cell survival and tissue repair. Inflamm. Res. 61, 233–244 (2012). https://doi.org/10.1007/s00011-011-0405-7

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  • DOI: https://doi.org/10.1007/s00011-011-0405-7

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