IL-24 is expressed during wound repair and inhibits TGFalpha-induced migration and proliferation of keratinocytes.

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.

journal_name

Exp Dermatol

journal_title

Experimental dermatology

authors

Poindexter NJ,Williams RR,Powis G,Jen E,Caudle AS,Chada S,Grimm EA

doi

10.1111/j.1600-0625.2010.01077.x

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

714-22

issue

8

eissn

0906-6705

issn

1600-0625

pii

EXD1077

journal_volume

19

pub_type

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