MMP-21 is expressed by macrophages and fibroblasts in vivo and in culture.
Matrix metalloproteinase (MMP)-21 and MMP-26 (matrilysin-2) are two recently cloned epithelial metalloproteases. Here we examined their expression in various benign skin disorders, in which macrophages and fibroblasts have been implicated as well as in cultures of these cells. Expression of MMP-21 was detected by immunohistochemistry in a subset of macrophages of granulomatous skin lesions and in fibroblasts in dermatofibromas. MMP-21 mRNA was found in THP-1, U937, HEL 299 and Hs68 cells. Furthermore, MMP-21 protein was detected by immunohistochemistry in cultures of the same cell lines. In culture MMP-21 was upregulated by phorbol myristate acetate in THP-1 cells and by retinoic acid (RA) in U937 cells, and downregulated by transforming growth factor beta 1 (TGF-beta1) in HEL 299 as assessed by Taqman quantitative polymerase chain reaction (PCR). Expression of MMP-26 was detected by immunohistochemistry in granulomatous skin diseases and actinic elastosis. MMP-26 at both mRNA and protein levels was only found in HEL 299 cells. In culture it was downregulated by TGF-beta1, RA and IL-1beta as assessed by Taqman quantitative PCR. Our results suggest these two novel MMPs are not only associated with cancer but may be important in connective tissue remodelling and pathobiology of various benign skin disorders.
Skoog
Tiina
T
Clinical Research Center, Novum, Karolinska University Hospital, and Department of Biosciences and Nutrition, Karolinska Institutet, Novum, S-14157 Huddinge, Sweden. tiina.skoog@biosci.ki.se
Ahokas
Katja
K
Orsmark
Christina
C
Jeskanen
Leila
L
Isaka
Keiichi
K
Saarialho-Kere
Ulpu
U
D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000494:pharmacology; D007641:Keratolytic Agents / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics* / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012871:Skin Diseases / Q000378:metabolism* / Q000503:physiopathology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D053583:Interleukin-1beta; D007641:Keratolytic Agents; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014212:Tretinoin; C016658:phorbolol myristate acetate; C471969:MMP21 protein, human; C410599:MMP26 protein, human; D053505:Matrix Metalloproteinases, Secreted; D013755:Tetradecanoylphorbol Acetate