TY - JOUR
T1 - IL-24 is expressed during wound repair and inhibits TGFα-induced migration and proliferation of keratinocytes
AU - Poindexter, Nancy J.
AU - Williams, Ryan R.
AU - Powis, Garth
AU - Jen, Emily
AU - Caudle, Abigail S.
AU - Chada, Sunil
AU - Grimm, Elizabeth A.
PY - 2010/8
Y1 - 2010/8
N2 - 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 α (TGFα), TGFβ, IFNγ, and IFNβ, 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 TGFα-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.
AB - 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 α (TGFα), TGFβ, IFNγ, and IFNβ, 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 TGFα-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.
KW - Cytokines
KW - Interleukin-24
KW - Keratinocyte
KW - Wound repair
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UR - http://www.scopus.com/inward/citedby.url?scp=77954851839&partnerID=8YFLogxK
U2 - 10.1111/j.1600-0625.2010.01077.x
DO - 10.1111/j.1600-0625.2010.01077.x
M3 - Article
C2 - 20545760
AN - SCOPUS:77954851839
SN - 0906-6705
VL - 19
SP - 714
EP - 722
JO - Experimental dermatology
JF - Experimental dermatology
IS - 8
ER -