Ultraviolet radiation-induced cytokines promote mast cell accumulation and matrix metalloproteinase production: potential role in cutaneous lupus erythematosus.
OBJECTIVE
To examine the role of mast cells (MCs), cytokines, and matrix metalloproteinases (MMPs) following ultraviolet B (UVB) radiation in cutaneous lupus erythematosus (CLE).


METHODS
Immunohistochemistry was used to determine the presence of MCs and the expression of MMP-1, MMP-9, interleukin (IL)-15, and CCL5/RANTES in skin from patients with CLE. Human keratinocytes were exposed to varying doses of UVB and supernatants were collected and assessed for IL-15, CCL5, MMP-1, and MMP-9 by protein assays. MC migration was determined against supernatants from UVB-treated keratinocytes.


RESULTS
MCs in the skin of patients with CLE were significantly increased. MMP-1 and MMP-9 expression was abundant in these lesions. Intense reactivity for IL-15 and CCL5 was found in skin, particularly in epidermal keratinocytes, from patients with CLE. UVB irradiation induced IL-15, CCL5, MMP-1, and MMP-9 production from keratinocytes in a dose- and time-dependent manner. Supernatants obtained from UVB-treated keratinocytes induced MC migration, which was attenuated by anti-IL-15 and anti-CCL5 neutralizing antibodies. IL-15 induced MC-derived MMP production.


CONCLUSIONS
Our results indicate that MCs and MMPs may play a role in the skin inflammation in CLE. MC recruitment as well as MMP production may be perpetuated by UV irradiation through locally released mediators.
Infection and Inflammation Research Centre, Department of Pathology, School of Medical Sciences, University of New South Wales, Sydney, Australia.
H
H
Van Nguyen
N
N
Di Girolamo
N
N
Jackson
T
T
Hampartzoumian
P
P
Bullpitt
N
N
Tedla
D
D
Wakefield
D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000528:radiation effects; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008178:Lupus Erythematosus, Cutaneous / Q000378:metabolism* / Q000473:pathology; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D014020:Tissue Extracts / Q000494:pharmacology; D014466:Ultraviolet Rays
D015415:Biomarkers; D016207:Cytokines; D014020:Tissue Extracts; D020782:Matrix Metalloproteinases