The kinase p38 alpha serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression

Chun Kim, Yasuyo Sano, Kristina Todorova, Bradley A. Carlson, Luis Arpa, Antonio Celada, Toby Lawrence, Kinya Otsu, Janice L. Brissette, J. Simon C. Arthur, Jin Mo Park

    Research output: Contribution to journalArticlepeer-review

    191 Citations (Scopus)

    Abstract

    The mitogen-activated protein kinase p38 mediates cellular responses to injurious stress and immune signaling. Among the many p38 isoforms, p38 alpha is the most widely expressed in adult tissues and can be targeted by various pharmacological inhibitors. Here we investigated how p38 alpha activation is linked to cell type-specific outputs in mouse models of cutaneous inflammation. We found that both myeloid and epithelial p38 alpha elicit inflammatory responses, yet p38 alpha signaling in each cell type served distinct inflammatory functions and varied depending on the mode of skin irritation. In addition, myeloid p38 alpha 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 alpha in the regulation of inflammation and show mixed potential for its inhibition as a therapeutic strategy.

    Original languageEnglish
    Pages (from-to)1019-1027
    Number of pages9
    JournalNature Immunology
    Volume9
    Issue number9
    DOIs
    Publication statusPublished - Sep 2008

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