Article abstract
Nature Immunology 9, 1019 - 1027 (2008)
Published online: 1 August 2008 | doi:10.1038/ni.1640
The kinase p38
serves cell type–specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression
Chun Kim1, Yasuyo Sano1, Kristina Todorova1, Bradley A Carlson2, Luis Arpa3, Antonio Celada3, Toby Lawrence4, Kinya Otsu5, Janice L Brissette1, J Simon C Arthur6 & Jin Mo Park1
Abstract
The mitogen-activated protein kinase p38 mediates cellular responses to injurious stress and immune signaling. Among the many p38 isoforms, p38
is the most widely expressed in adult tissues and can be targeted by various pharmacological inhibitors. Here we investigated how p38 activation is linked to cell type–specific outputs in mouse models of cutaneous inflammation. We found that both myeloid and epithelial p38 elicit inflammatory responses, yet p38 signaling in each cell type served distinct inflammatory functions and varied depending on the mode of skin irritation. In addition, myeloid p38 limited acute inflammation via activation of anti-inflammatory gene expression dependent on mitogen- and stress-activated kinases. Our results suggest a dual function for p38 in the regulation of inflammation and show mixed potential for its inhibition as a therapeutic strategy.
- Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
- Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Macrophage Biology Group, Institute for Research in Biomedicine and University of Barcelona, 08028 Barcelona, Spain.
- Centre for Translational Oncology, Institute of Cancer and CR-UK Clinical Centre, Barts and The London Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK.
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita Osaka 565-0871, Japan.
- Medical Research Council Protein Phosphorylation Unit, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, UK.
Correspondence to: Jin Mo Park1 e-mail: jmpark@cbrc2.mgh.harvard.edu
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