Abstract |
Interleukin (IL)-24 is the protein product of melanoma differentiation-associated gene 7 (MDA-7). Originally identified as a tumor suppressor molecule, MDA-7 was renamed IL-24 and classified as a cytokine because of its chromosomal location in the IL-10 locus, its mRNA expression in leukocytes, and its secretory sequence elements. We previously reported that IL-24 is expressed by cytokine-activated monocytes and T lymphocytes. Here, we show that IL-24 is expressed in keratinocytes during wound repair. Paraffin-embedded tissues prepared from human skin sampled at days 2, 6, and 10 after wounding were examined by immunohistochemistry for the expression of IL-24. Protein expression was detected in the keratinocyte population with maximum expression at days 2 and 6, and no expression by day 10 (four of four subjects). In vitro studies showed that cytokines involved in wound repair, most notably transforming growth factor alpha ( TGFalpha), TGFbeta, IFNgamma, and IFNbeta, upregulated IL-24 protein expression in normal human epidermal keratinocytes (NHEKs). Examination of the function of IL-24 in both in vitro wound repair and migration assays demonstrated that IL-24 inhibits TGFalpha-induced proliferation and migration of NHEKs. These data support the hypothesis that IL-24 functions during an inflammatory response in the skin by inhibiting the proliferation and migration of keratinocytes.
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Authors | Nancy J Poindexter, Ryan R Williams, Garth Powis, Emily Jen, Abigail S Caudle, Sunil Chada, Elizabeth A Grimm |
Journal | Experimental dermatology
(Exp Dermatol)
Vol. 19
Issue 8
Pg. 714-22
(Aug 2010)
ISSN: 1600-0625 [Electronic] Denmark |
PMID | 20545760
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Interleukins
- Transforming Growth Factor alpha
- Transforming Growth Factor beta
- interleukin-24
- Interferon-beta
- Interferon-gamma
- EGFR protein, human
- ErbB Receptors
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Topics |
- Adult
- Biopsy
- Cell Movement
(physiology)
- Cell Proliferation
- Cells, Cultured
- ErbB Receptors
(metabolism)
- Humans
- Interferon-beta
(metabolism)
- Interferon-gamma
(metabolism)
- Interleukins
(metabolism)
- Keratinocytes
(cytology, metabolism)
- Macrophages
(cytology, metabolism)
- Phosphorylation
- Transforming Growth Factor alpha
(metabolism)
- Transforming Growth Factor beta
(metabolism)
- Wound Healing
(physiology)
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